Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([C@@H:4]1[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:5]1)=[N+]=[N-].CCO.C(N(CC)C(C)C)(C)C.[CH3:32][C:33]([CH:35]1[C:41](=[O:42])[CH2:40][C:39]([CH3:44])([CH3:43])[CH2:38][C:36]1=[O:37])=O>CO.[Pd]>[CH3:44][C:39]1([CH3:43])[CH2:40][C:41](=[O:42])[C:35](=[C:33]([NH:1][C@@H:4]2[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]3[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]3=[O:13])[CH2:5]2)[CH3:32])[C:36](=[O:37])[CH2:38]1
Reactant: CC(=O)C1C(=O)CC(C)(C)CC1=O
Reactant: Cc1cn([C@H]2C[C@H](N=[N+]=[N-])[C@@H](CO)O2)c(=O)[nH]c1=O
Agent: [Pd]
Solvent: CO
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: CC(N[C@H]1C[C@H](n2cc(C)c(=O)[nH]c2=O)O[C@@H]1CO)=C1C(=O)CC(C)(C)CC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 65.8 %

Procedure:
3′-Deoxy-3′-azido-thymidine (200 mg, 0.75 mmol) was dissolved in MeOH (25 ml) and Pd/C (40 mg) was added. The suspension was stirred over a constant stream of H2 overnight. The reaction mixture was filtered, and the filtrate was concentrated. The residue was taken up in abs. EtOH (5 ml), N,N-diisopropylethylamine (0.1 ml) and 2-acetyldimedone (204 mg, 1.12 mmol) were added and the solution was refluxed for 5 h. The reaction mixture was cooled to room temperature and the product was precipitated by adding ether (50 ml) giving 3′-deoxy-3′-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-ethylamino]-thymidine (24) (200 mg, 66%).
Reaction SMILES: CCOC(/N=N/C(OCC)=O)=O.[CH3:13][O:14][C:15]([C:17]1[S:18][CH:19]=[CH:20][C:21]=1[OH:22])=[O:16].[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH:30](O)[CH3:31].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH:30]([O:22][C:21]1[CH:20]=[CH:19][S:18][C:17]=1[C:15]([O:14][CH3:13])=[O:16])[CH3:31]
Reactant: COC(=O)c1sccc1O
Reactant: CC(O)c1ccccc1Cl
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1sccc1OC(C)c1ccccc1Cl
Temperature: 25 °C
Yield: 50.6 %

Procedure:
DEAD (2.6 mL, 16.4 mmol, 1.3 Eq.) was added dropwise to a stirred solution of methyl-3-hydroxythiophene-2-carboxylate (2.0 g, 12.6 mmol, 1.0 Eq.), 1-(2-chlorophenyl)ethanol (2.57 g, 16.4 mmol, 1.3 Eq.) and triphenylphosphine (4.31 g, 16.4 mmol, 1.3 Eq.) in anhydrous THF (30 mL) at 0° C. under nitrogen. The reaction was allowed to warm to ambient temperature overnight. The crude reaction mixture was absorbed onto SiO2 and purified by column chromatography eluting with 0 to 10% EtOAc/petroleum ether to give the sub-title compound as a white solid (1.89 g, 6.37 mmol, 50%); 1H NMR (400 MHz, CDCl3) δ 1.72 (3H, d), 3.87 (3H, s), 5.78 (1H, quint), 6.65 (1H, d), 7.21-7.32 (3H, m), 7.38 (1H, dd), 7.55 (1H, dd).
Reaction SMILES: Br[C:2]1[C:3]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)=[CH:4][C:5]2[N:6]([C:9](=[O:23])[N:10]([CH2:12][C:13]3[CH:14]=[N:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=3)[N:11]=2)[C:7]=1[CH3:8].[C:31]1(B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.CC1C(CN2C(=O)N3C=CC(C4C=CC(C#N)=CC=4)=C(C4C=CC=CC=4)C3=N2)=CC=C(C(F)(F)F)N=1>>[Cl:30][C:27]1[CH:26]=[CH:25][C:24]([C:3]2[C:2]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[C:7]([CH3:8])[N:6]3[C:9](=[O:23])[N:10]([CH2:12][C:13]4[CH:14]=[N:15][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:17][CH:18]=4)[N:11]=[C:5]3[CH:4]=2)=[CH:29][CH:28]=1
Reactant: OB(O)c1ccccc1
Reactant: Cc1c(Br)c(-c2ccc(Cl)cc2)cc2nn(Cc3ccc(C(F)(F)F)nc3)c(=O)n12
Agent: Cc1nc(C(F)(F)F)ccc1Cn1nc2c(-c3ccccc3)c(-c3ccc(C#N)cc3)ccn2c1=O
Product: Cc1c(-c2ccccc2)c(-c2ccc(Cl)cc2)cc2nn(Cc3ccc(C(F)(F)F)nc3)c(=O)n12
Yield: 68.7 %

Procedure:
The title compound (17 mg, 68%) as a light yellow powder was prepared from 6-bromo-7-(4-chlorophenyl)-5-methyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (25 mg, 0.05 mmol) and phenylboronic acid (25 mg, 0.2 mmol) by procedures analogous to those used for the preparation of 4-(2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-oxo-8-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridin-7-yl)benzonitrile. HPLC/MS: retention time=4.14 min, [M+H]+=495.3.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][N:6]2[C:11]([C:12]([F:15])([F:14])[F:13])=[CH:10][C:9]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)=[N:8][C:7]=12)#[CH:2].Br[C:27]1[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=1>>[N:29]1[CH:30]=[CH:31][CH:32]=[C:27]([C:2]#[C:1][C:3]2[CH:4]=[N:5][N:6]3[C:11]([C:12]([F:14])([F:13])[F:15])=[CH:10][C:9]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=4)=[N:8][C:7]=23)[CH:28]=1
Reactant: Brc1cccnc1
Reactant: C#Cc1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Product: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)n3ncc(C#Cc4cccnc4)c3n2)cc1

Procedure:
The title compound was prepared from 3-ethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.1) (355 mg, 1.0 mmol) and 3-bromopyridine [CAS 626-55-1; commercially available] (158 mg, 1.0 mmol) according to general procedure II. Obtained as an orange solid (94 mg, 22%). MS (ISP) 433.3 [(M+H)+]; mp 187–188° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.[CH3:12][C:13]1(C)[O:20][C:18](=O)[CH2:17][C:15](=O)[O:14]1.C1CCC(N=C=NC2CCCCC2)CC1.C(O)C=C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9](=[O:11])[CH2:12][C:13]([O:14][CH2:15][CH:17]=[CH2:18])=[O:20])=[CH:6][CH:7]=1
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: O=C(O)Cc1ccc(F)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: C=CCO
Solvent: ClCCl
Product: C=CCOC(=O)CC(=O)Cc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 95 %

Procedure:
To a CH2Cl2 (210 mL) solution of 4-fluorophenyl acetic acid (32.28 g, 209.42 mmol) at 0° C. was added DMAP (25.58 g, 209.42 mmol), and Meldrum's Acid (30.18 g, 209.42 mmol) followed by DCC (43.21 g, 209.42 mmol). The reaction mixture was warmed to ambient temperature and stirred for 4 h. The reaction was filtered to remove the DCU and the filtrate washed with 1N HCl, H2O, and brine. The organics were dried (Na2SO4), filtered and concentrated to a yellow oil. The residue was redissolved in THF (200 mL) and allyl alcohol (14.38 mL, 211.51 mmol). The reaction mixture was refluxed for 3 h and then concentrated to deliver 47 g (95% yield) of the title compound as a pale yellow oil and used without further purification.
Reaction SMILES: [C:1]1([SH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11](Br)[N:10]=1>O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C.O>[Br:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([S:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:10]=1
Reactant: Sc1ccccc1
Reactant: Brc1cccc(Br)n1
Solvent: O
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: C1CCOC1
Product: Brc1cccc(Sc2ccccc2)n1
Reaction time: 8 h

Procedure:
To sodium hydride, 0.91 g, (22.3 mmol) (washed with hexane) is added, under nitrogen, 8 ml of tetrahydrofuran. The suspension is then cooled in an ice bath. Thiophenol (2.32 g, 21.1 mmol) in 8 ml of tetrahydrofuran is added dropwise over 30 minutes, after which 4 ml of hexamethylphosphorictriamide is added. The solution is added dropwise over 15 hr to 5 g (21.1 mmol) 2,6-dibromopyridine in 8 ml tetrahydrofuran and 2 ml hexamethylphosphorictriamide at 24°. The reaction mixture is stirred overnight under nitrogen. After addition of 2 ml hexamethylphosphorictriamide, the solution is refluxed for 3 days, then diluted with water and extracted with ether, washed with 5% sodium hydroxide (2×), water (3×) and brine, dried over magnesium sulfate and concentrated. The residue is finally washed with 100 ml cold (ice bath) hexane to give 2-bromo-6-phenylthiopyridine, m.p. 47°.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([CH:38]=CC=1)/[CH:6]=[C:7]1\[CH2:8][C@@H:9]2[C@H:13]([CH2:14]\1)[C@H:12](/[CH:15]=[CH:16]/[C@@H:17]([O:24]C1CCCCO1)[CH:18]([CH3:23])[CH2:19][C:20]#[C:21][CH3:22])[C@H:11]([O:31]C1CCCCO1)[CH2:10]2)=O.[CH3:41][C:42]([CH3:44])=[O:43].O=[Cr](=O)=O.C1C=CC=CN=1.C1C=CC=CN=1.CCOCC>ClCCl>[C:42]([C:44]1[CH:38]=[C:5]([CH:4]=[CH:3][CH:1]=1)/[CH:6]=[C:7]1\[CH2:8][C@@H:9]2[C@H:13]([CH2:14]\1)[C@H:12](/[CH:15]=[CH:16]/[C@@H:17]([OH:24])[CH:18]([CH3:23])[CH2:19][C:20]#[C:21][CH3:22])[C@H:11]([OH:31])[CH2:10]2)(=[O:43])[CH3:41]
Reactant: CC#CCC(C)[C@@H](/C=C/[C@H]1[C@H]2C/C(=C/c3cccc(C=O)c3)C[C@H]2C[C@H]1OC1CCCCO1)OC1CCCCO1
Reactant: CC(C)=O
Agent: O=[Cr](=O)=O
Solvent: CCOCC
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC#CCC(C)[C@H](O)/C=C/[C@H]1[C@H]2C/C(=C/c3cccc(C(C)=O)c3)C[C@H]2C[C@H]1O
Reaction time: 0.25 h

Procedure:
In order to convert the thus-obtained carbinol into the methyl ketone, the residue is dissolved in 50 ml of dichloromethane and this solution is added to 6 g of Collins reagent in 80 ml of dichloromethane. After 15 minutes, the mixture is combined with 300 ml of ether, filtered, and the filtrate washed in succession with water, 5% sodium bicarbonate solution, 10% strength sulfuric acid, and water, dried over magnesium sulfate, and evaporated under vacuum.
Reaction SMILES: [O:1]=[C:2]1[NH:6][C:5](=[O:7])[CH:4]([CH2:8][C:9]2[CH:21]=[CH:20][C:12]([O:13][CH2:14][C:15]([O:17]CC)=[O:16])=[CH:11][CH:10]=2)[S:3]1.C([O-])([O-])=O.[Na+].[Na+]>CO.O>[O:1]=[C:2]1[NH:6][C:5](=[O:7])[CH:4]([CH2:8][C:9]2[CH:21]=[CH:20][C:12]([O:13][CH2:14][C:15]([OH:17])=[O:16])=[CH:11][CH:10]=2)[S:3]1
Reactant: CCOC(=O)COc1ccc(CC2SC(=O)NC2=O)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=C(O)COc1ccc(CC2SC(=O)NC2=O)cc1
Temperature: 27.5 °C
Reaction time: 5 h
Yield: 79 %

Procedure:
To a stirred solution of ethyl [4-[[2,4-dioxo-1,3-thiazolidine-5-yl]methyl]phenoxy]acetate (110 g, 0.36 mol) in methanol (0.65 L) was added as solution of Na2CO3 (200 g, 1.88 mol) in water (0.65 L) and stirred for 5 h at 25 to 30° C. After completion of the reaction, methanol was removed under reduced pressure; water was added to the residue and was acidified with hydrochlori acid. The precipitated white solid was filtered and dired to yield the title compound (80 g, 80%). mp: 181-183° C.
Reaction SMILES: P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1F.O1CCOCC1.[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>C(Cl)Cl.CN(C=O)C>[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1
Reactant: C1COCCN1
Reactant: Fc1cc(C(F)(F)F)ccc1Br
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: FC(F)(F)c1ccc(Br)c(N2CCOCC2)c1
Temperature: 150 °C
Yield: 36 %

Procedure:
A microwave vial charged with potassium phosphate (0.533 g, 2.51 mmol), 1-bromo-2-fluoro-4-(trifluoromethyl)benzene (0.610 g, 2.51 mmol) and 1 mL dioxane, was treated with morpholine (0.437 ml, 5.02 mmol) and was heated to 150° C. in a microwave reactor for one hour. LC/MS showed mostly starting material, so the reaction mixture was treated with 1 mL DMF and was heated to 150° C. in an oil bath overnight. LC/MS showed product, so the reaction mixture was diluted with DCM, filtered through a syringe filter, and concentrated. Purification of the resulting residue by silica gel column chromatography (0 to 50% EtOAc/heptane) gave 4-(2-bromo-5-(trifluoromethyl)phenyl)morpholine (0.280 g, 0.903 mmol) as a clear oil. [M+H]+=312.0
Reaction SMILES: [CH:1]1([O:6][C:7]2[C:12]3[O:13][C:14]([CH3:16])=[CH:15][C:11]=3[C:10]([CH:17]=[O:18])=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.S(=O)(=O)([OH:21])N.Cl([O-])=O.[Na+]>CC(C)=O.O>[CH:1]1([O:6][C:7]2[C:12]3[O:13][C:14]([CH3:16])=[CH:15][C:11]=3[C:10]([C:17]([OH:21])=[O:18])=[CH:9][CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: NS(=O)(=O)O
Reactant: Cc1cc2c(C=O)ccc(OC3CCCC3)c2o1
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: O
Solvent: CC(C)=O
Product: Cc1cc2c(C(=O)O)ccc(OC3CCCC3)c2o1
Temperature: 0 °C
Reaction time: 5.5 h
Yield: 68.3 %

Procedure:
To a well stirred solution of 7-cyclopentyloxy-2-methylbenzo[b]furan-4-carboxaldehyde (55.0 g, 0.225 moles), sulphamic acid (76.0 g, 0.787 moles) in acetone (600 mL) was added a solution of sodium chlorite (51.0 g, 0.562 moles) in water (150 mL) at 0-5° C. and stirred for 5-6 hrs. Ice cold water (1.0 L) was added to reaction mixture; solid separated was filtered and purified by acid-base technique to get 40.0 g of pure product.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]1[C:16]([CH2:17][CH2:18][C:19]([OH:21])=O)=[CH:15][CH:14]=[C:13]([C:22]3[C:23]([N:42]([CH3:47])[S:43]([CH3:46])(=[O:45])=[O:44])=[CH:24][C:25]4[O:29][C:28]([C:30]5[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=5)=[C:27]([C:37](=[O:40])[NH:38][CH3:39])[C:26]=4[CH:41]=3)[N:12]=1)[NH:6]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:11]4[N:12]=[C:13]([C:22]5[C:23]([N:42]([CH3:47])[S:43]([CH3:46])(=[O:44])=[O:45])=[CH:24][C:25]6[O:29][C:28]([C:30]7[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=7)=[C:27]([C:37]([NH:38][CH3:39])=[O:40])[C:26]=6[CH:41]=5)[CH:14]=[CH:15][C:16]=4[CH2:17][CH2:18][C:19](=[O:21])[N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc(CCC(=O)O)c(-c4cc5c(F)cccc5[nH]4)n3)cc12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3C(=O)CC4)cc12

Procedure:
To a mixture of 3-(2-(4-fluoro-1H-indol-2-yl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-3-yl)propanoic acid (88 mg, 0.133 mmol) and HATU (126 mg, 0.333 mmol) in DMF (6650 μl) was added DIEA (116 μl, 0.665 mmol). The resultant mixture was stirred for 1 h at ambient temperature then was diluted with EtOAc and washed successively with H2O (3×) and brine (1×). The organic layer was dried over MgSO4, filtered, concentrated in vacuo, and the residue purified by silica gel column chromatography using a gradient of 0-30% EtOAc/CH2Cl2 as eluent. 1H NMR δ (ppm) (CHCl3-d): 8.38 (1H, d, J=8.46 Hz), 8.12 (1H, s), 8.02 (2H, dd, J=8.55, 5.32 Hz), 7.69 (3H, d, J=9.74 Hz), 7.60 (1H, d, J=7.80 Hz), 7.36 (1H, td, J=8.24, 5.56 Hz), 7.25 (2H, t, J=8.60 Hz), 7.02 (1H, t, J=8.68 Hz), 5.95 (1H, br s), 3.35 (3H, s), 3.27˜3.22 (2H, m), 3.20˜3.15 (2H, m), 3.05 (3H, d, J=4.90 Hz), 2.85 (3H, s). MS (M+H)+: 641.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:5](=[O:8])[NH:6][CH:7]=1.[C:13]1(B(O)O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:5](=[O:8])[N:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=1
Reactant: COC(=O)c1cc(Br)c[nH]c1=O
Reactant: OB(O)c1ccccc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)c1cc(Br)cn(-c2ccccc2)c1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 86.4 %

Procedure:
A round bottom flask was charged with methyl 5-bromo-2-oxo-1,2-dihydropyridine-3-carboxylate (0.500 g, 2.2 mmol), phenylboronic acid (0.66 g, 5.4 mmol), and copper(II) acetate (0.78 g, 4.3 mmol). Dichloromethane (25 mL) was added, followed by 4 A molecular sieves (500 mg, activated) and pyridine (0.70 mL, 8.6 mmol). The reaction mixture was stirred overnight at room temperature in the presence of air. The reaction mixture was diluted with dichloromethane and filtered through a small pad of Celite, washing well with dichloromethane. The filtrate was concentrated under vacuum. The remaining residue was purified by silica gel chromatography (1% methanol/dichloromethane) to give methyl 5-bromo-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxylate as a yellow foam/oil (0.655 g, 1.9 mmol, 89% yield). MS (ESI pos. ion) m/z: 309 (MH+). Calc'd exact mass for C13H10BrNO3: 308.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=1[N+:18]([O-:20])=[O:19])[CH2:12]CN)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:21]([N:23](CC)CC)C.[C:28]1([S:34](Cl)(=[O:36])=[O:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=1[N+:18]([O-:20])=[O:19])[CH2:12][N:23]([CH3:21])[S:34]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)(=[O:36])=[O:35])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCN(CC)CC
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: NCCc1ccc([N+](=O)[O-])c(OCc2ccccc2)c1
Solvent: ClCCl
Product: CN(Cc1ccc([N+](=O)[O-])c(OCc2ccccc2)c1)S(=O)(=O)c1ccccc1
Temperature: 25 °C

Procedure:
To a solution of (3-benzyloxy-4-nitrobenzyl)methylamine (1.00 g, 3.672 mmol) and triethylamine (0.56 mL, 4.04 mmol) in CH2Cl2 (20 mL) is added dropwise benzenesulfonyl chloride (0.515 mL, 4.04 mmol) and the reaction is heated at reflux for 1 h. After cooling to RT, the reaction is diluted with CH2Cl2 (75 mL). The solution is washed with 1N HCl, saturated sodium bicarbonate, dried over Na2SO4, filtered, and concentrated under vacuum to afford an orange oil. The oil is triturated with ether to afford the title compound: (M+1)+=413.
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][C:10](C)([O-])[CH3:11].[K+].C(Br)C=C.O>O1CCCC1>[CH2:1]([O:8][CH2:11][CH:10]=[CH2:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1ccccc1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: C=CCBr
Solvent: O
Solvent: C1CCOC1
Product: C=CCOCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In 870 g of tetrahydrofuran were dissolved 218 g (2 mol) of benzyl alcohol and 224 g (2 mol) of potassium t-butoxide. With stirring at room temperature, 242 g (2 mol) of allyl bromide was added dropwise so that the temperature might not exceed 60° C. At the end of addition, the solution was heated at 60° C. on an oil bath and ripened for one hour at the temperature. The solution was allowed to cool down to room temperature, and 11.2 g (0.1 mol) of potassium t-butoxide was added. With stirring at room temperature, 12.1 g (0.1 mol) of allyl bromide was added dropwise. The solution was heated at 60° C. on an oil bath and ripened for one hour at the temperature. The solution was cooled in an ice bath, and 550 g of water was added. The organic layer was collected. The solvent was distilled off in vacuum, yielding 299 g of a crude end product. The product was used -in the subsequent reaction without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([N+:16]([O-:18])=[O:17])=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][NH:7][C:6]2=O.[Cl:19][C:20]1[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=1>O=S(Cl)Cl.CN(C=O)C>[Cl:19][C:20]1[CH:26]=[CH:25][C:23]([NH:24][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[C:4]=3[N+:16]([O-:18])=[O:17])[N:9]=[CH:8][N:7]=2)=[CH:22][CH:21]=1
Reactant: COc1cc2nc[nH]c(=O)c2c([N+](=O)[O-])c1OC
Reactant: Nc1ccc(Cl)cc1
Solvent: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: COc1cc2ncnc(Nc3ccc(Cl)cc3)c2c([N+](=O)[O-])c1OC
Temperature: 90 °C
Reaction time: 3 h

Procedure:
To a solution of 6,7-dimethoxy-5-nitro-3H-quinazolin-4-one (0.5 g, 1.99 mmol) (from Example 1, Step A, supra) in SOCl2 (20 mL) (Aldrich) was added a few drops of DMF (0.05 mL). The reaction mixture was then heated with stirring at 90° C. for 3 hours. The solvents were evaporated and the residue was dried in vacuo. This residue was dissolved in 2-propanol (30 mL), then 4-chloroaniline (0.25 g, 1.99 mmol) (Aldrich) was added. The reaction mixture was heated at 110° C. for 3 hours. The solvents were removed and the residue was purified by chromatography using EtOAc/CH2Cl2/NEt3 (1:2:0.05) as eluent to give the desired (4-chloro-phenyl)-(6,7-dimethoxy-5-nitro-quinazolin-4-yl)-amine as a yellow solid. (Yield 0.5 g, 70%).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[C:10]1([CH3:18])[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[Mg]Cl>C1CC=CCCC=C1.C1CC=CCCC=C1.[Ni].C1COCC1>[C:10]1([CH3:18])[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1
Reactant: COc1ccc(Cl)cc1
Reactant: Cc1ccccc1[Mg]Cl
Agent: [Ni]
Agent: C1=C\CC/C=C\CC/1
Solvent: C1=CCCC=CCC1
Solvent: C1CCOC1
Product: COc1ccc(-c2ccccc2C)cc1
Reaction time: 0.17 h
Yield: 45 %

Procedure:
In the drybox, 54.0 mg (0.303 mm) of (Me3C)2PH(S) (from Experiment 18), 83.4 mg (0.303 mm) of Ni(COD)2 and 10.0 mL of THF were loaded into a reactor (20 mL) equipped with a magnetic stir bar. The resulting mixture was stirred at room temperatureover a period of 10 min. After addition of 1.43 g (10.0 mm) of 4-chloroanisol, the resulting mixture was stirred for 5 min until the catalytic reaction was initiated by dropwise addition of 15 mL (15.0 mm, 1.0 M in THF) of o-tolylmagnesium chloride at room temperature over a period of 5 min. The resulting mixture was stirred at room temperature over 12 h before the reaction was quenched with 10.0 mL of H2O, and the mixture was diluted with 300 mL of Et2O. After separation of organic and aqueous phases, the organic phase was washed with 2×100 mL of H2O, and 100 mL of brine, then dried over mgSO4, filtered and concentrated by rotary evaporation. The crude product was purified by column chromatography on silica gel (100:1-hexane:methyl t-butyl ether) to afford 0.90 g (45% yield) of 4-(o-tolyl)anisole.
Reaction SMILES: [H][H].[F:3][C@H:4]1[CH2:9][C@H:8]2[C@H:10]3[C@H:20]([CH2:21][CH2:22][C@:6]2([CH3:7])[C:5]1=[O:23])[C@:18]1([CH3:19])[C@H:13]([CH2:14][CH2:15][CH2:16][CH2:17]1)[CH2:12][CH2:11]3.CO.[OH-].[K+]>C(O)C.[Pd]>[F:3][C@H:4]1[CH2:9][C@H:8]2[C@H:10]3[C@H:20]([CH2:21][CH2:22][C@:6]2([CH3:7])[C:5]1=[O:23])[C@:18]1([CH3:19])[C@@H:13]([CH2:14][CH2:15][CH2:16][CH2:17]1)[CH2:12][CH2:11]3
Reactant: C[C@]12CCCC[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)[C@@H](F)C[C@@H]12
Reactant: [H][H]
Agent: [Pd]
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: CO
Product: C[C@]12CCCC[C@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)[C@@H](F)C[C@@H]12

Procedure:
250 mg of 16β fluoro-5-α-androsten-17-one in 50 ml of ethanol was treated with 50 mg of 5% palladium on carbon and hydrogen gas for 21/2hours. The reaction mixture, as indicated by the IR, is compatible with 16β-fluoro-5α-androstan-17-one. This crude product was treated with 5 ml methanol and 5 ml of 1N methanolic KOH for one hour. The mixturewas partitioned between methylene chloride and water and subjected to HPLC as indicated above. Crystallization of the less mobile component from methanol gave 30 mg of 16β-fluoro-5β-androstan-17-one as prismatic needles, melting point 148°-150° C.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.C(Cl)(=O)C(Cl)=O.[CH2:17]([NH:19][CH2:20][CH3:21])[CH3:18]>O1CCCC1.CN(C)C=O.C(OCC)(=O)C>[CH2:17]([N:19]([CH2:20][CH3:21])[C:5](=[O:7])[C:4]1[CH:8]=[CH:9][CH:10]=[C:2]([I:1])[CH:3]=1)[CH3:18]
Reactant: CCNCC
Reactant: O=C(O)c1cccc(I)c1
Agent: O=C(Cl)C(=O)Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCN(CC)C(=O)c1cccc(I)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.7 %

Procedure:
3-Iodobenzoic acid (55.5 g, 0.224 mol) was dissolved in tetrahydrofuran (220 mL) and oxalyl chloride (22 mL, 0.252 mol). Catalytic dimethylformamide (4 drops) was added, the solution was stirred at room temperature for 1 hour, and the solvent was removed under vacuum. The residue was dissolved in 220 mL petroleum ether (35°-60° C. boiling range) and cooled to 0° C. in an ice bath. Diethylamine (55 mL, 0.532 mol) was then added dropwise over 15 minutes. The reaction mixture was stirred an additional 15 minutes in the ice bath, then diluted with ethyl acetate (100 mL) and washed with saturated sodium chloride solution (50 mL). The organic layer was separated, dried over magnesium sulfate, and concentrated in vacuo to approximately half of the original volume. The solution was then filtered through a small pad of silica gel, using ethyl acetate to wash the pad. All volatiles were removed in vacuo, and the product was dried under high vacuum to give 65.69 g (97%) of N,N-diethyl-3-iodobenzamide as an amber oil. NMR (300 MHz, CDCl3): δ 1.11 (br s, 3H); 1.21 (br s, 3H); 3.23 (br s, 2H); 3.51 (br s, 2H); 7.13 (ddd, J1 =0.8 Hz, J2 =7.6 Hz, J3 =7.6 Hz, 1H); 7.32 (ddd, J1 =1.3 Hz, J2 =1.3 Hz, J3 =7.5 Hz, 1H); 7.71 (d, J=1.2 Hz, 1H); 7.72 (ddd, J1 =1.3 Hz, J2 =1.3 Hz, J3 =approx. 8.0 Hz (partially obstructed), 1H). Mass spectrum (CI--CH4) m/e: 304 (M+1, 100%). Calc. for C11H14NOI: C, 43.58; H, 4.65; N, 4.62; I, 41.86. Found: C, 43.68; H, 4.64; N, 4.64; I, 41.92.