Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[C:15](=[O:16])[C:14]3=[C:17]([Cl:21])[CH:18]=[CH:19][CH:20]=[C:13]3[C:12]2=[O:22])[CH:5]=1)([O-])=O.[H][H]>[Ni].C(OCC)(=O)C>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[C:15](=[O:16])[C:14]3=[C:17]([Cl:21])[CH:18]=[CH:19][CH:20]=[C:13]3[C:12]2=[O:22])[CH:5]=1
Reactant: Cc1ccc([N+](=O)[O-])cc1N1C(=O)c2cccc(Cl)c2C1=O
Reactant: [H][H]
Agent: [Ni]
Solvent: CCOC(C)=O
Product: Cc1ccc(N)cc1N1C(=O)c2cccc(Cl)c2C1=O

Procedure:
The mixture of 1.65 g of N-(4-nitro-o-tolyl)-3-chlorophthalimide, 200 ml of ethyl acetate and 0.92 g of pre-washed Raney nickel is hydrogenated at 3.1 atm. and room temperature until the hydrogen uptake ceases. It is filtered, evaporated and the residue recrystallized from methanol, to yield the N-(4-amino-o-tolyl)-3-chlorophthalimide melting at 209°-211°.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[C:12]1[CH:13]=[C:14]([OH:18])[CH:15]=[CH:16][CH:17]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[C:19]([F:22])([F:21])[F:20].Br[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][C:32]([OH:34])=[O:33])=[CH:27][CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(Cl)Cl>[CH3:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[C:12]1[CH:13]=[C:14]([CH:15]=[CH:16][CH:17]=1)[O:18][CH2:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:31][C:32]([OH:34])=[O:33])=[CH:29][CH:30]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[C:19]([F:22])([F:20])[F:21]
Reactant: O=C(O)Cc1ccc(CBr)cc1
Reactant: Cc1cnc2c(C(F)(F)F)cccc2c1-c1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClCCl
Product: Cc1cnc2c(C(F)(F)F)cccc2c1-c1cccc(OCc2ccc(CC(=O)O)cc2)c1
Temperature: 70 °C
Reaction time: 8 h

Procedure:
3-[3-Methyl-8-(trifluoromethyl)quinolin-4-yl]phenol (1.13 g, 3.73 mmol) and 4-bromomethylphenylacetic acid (1.02 g, 4.47 mmol) in CH2Cl2 (60 mL) is treated with Cs2CO3 (4.86 g, 14.9 mmol) and the reaction is stirred overnight. The solvent is removed and the residue dissolved in THF and 2N aq NaOH. After heating at 70° C. for 1 h, the reaction is cooled and the layers separated. The aqueous layer is further extracted with ethyl acetate. The combined organics are dried (Na2SO4) and concentrated. The residue is chromatographed eluting with 20:80 ethyl acetate:hexane and then 5:95 methanol:methylene chloride to afford the title product.
Reaction SMILES: Cl.Cl.[OH:3][CH:4]([C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][C:18]=1[F:29])[CH2:5][CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH:8]1[C:13]([O:15][CH3:16])=[O:14].Br[CH2:31][CH2:32][S:33][C:34]1[S:35][CH:36]=[CH:37][CH:38]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C.CN(C=O)C.C(N(CC)CC)C>[OH:3][CH:4]([C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][C:18]=1[F:29])[CH2:5][CH2:6][CH:7]1[CH2:12][CH2:11][N:10]([CH2:31][CH2:32][S:33][C:34]2[S:35][CH:36]=[CH:37][CH:38]=2)[CH2:9][CH:8]1[C:13]([O:15][CH3:16])=[O:14]
Reactant: BrCCSc1cccs1
Reactant: COC(=O)C1CNCCC1CCC(O)c1c(F)cnc2ccc(OC)cc12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CN(C)C=O
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COC(=O)C1CN(CCSc2cccs2)CCC1CCC(O)c1c(F)cnc2ccc(OC)cc12
Temperature: 65 °C
Reaction time: 15 h
Yield: 46.6 %

Procedure:
0.74-cm3 of triethylamine was added to a solution composed of 1.17 g of methyl (3RS, 4RS)-4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate dihydrochloride in 20-cm3 of acetonitrile and 10 cm3 of DMF, followed by 638 mg of 2-(2-bromoethylthio)thiophene in 10 cm3 of acetonitrile, 1 g of potassium carbonate and 431 mg of potassium iodide. The mixture was stirred for 15 hours at a temperature in the region of 65° C. under an inert atmosphere. After cooling to about 20° C., the reaction mixture was filtered on sintered glass. The filtrate was taken up in 100-cm3 of acetonitrile and concentrated under reduced pressure (5 kPa). The residue was taken up in 200-cm3 of ethyl acetate and 100-cm3 of water. The organic phase was separated after settling out, washed with twice 75-cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography, under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45μ; diameter 2 cm; height 40 cm), eluting with a mixture of cyclohexane-ethyl acetate (25/75 by volume) and collecting 50-cm3 fractions. Fractions 6 to 8 were concentrated. 630 mg of methyl (3RS,4RS)-4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-carboxylate were obtained in the form of a colorless oil.
Reaction SMILES: B([C:4]1[CH:5]=[CH:6][C:7]([Cl:13])=[C:8]([CH:12]=1)[C:9]([OH:11])=[O:10])(O)O.I[C:15]1[CH:16]=[C:17]([B:21]([OH:23])[OH:22])[CH:18]=[CH:19][CH:20]=1.C([O-])([O-])=O.[K+].[K+].Cl>C1(C)C=CC=CC=1.CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[B:21]([C:17]1[CH:16]=[C:15]([C:4]2[CH:5]=[CH:6][C:7]([Cl:13])=[C:8]([C:9]([OH:11])=[O:10])[CH:12]=2)[CH:20]=[CH:19][CH:18]=1)([OH:23])[OH:22]
Reactant: O=C(O)c1cc(B(O)O)ccc1Cl
Reactant: OB(O)c1cccc(I)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CO
Solvent: Cc1ccccc1
Product: O=C(O)c1cc(-c2cccc(B(O)O)c2)ccc1Cl
Temperature: 75 °C

Procedure:
5-Borono-2-chlorobenzoic acid (200 mg, 1 mmol), 3-iodophenylboronic acid (125 mg, 0.5 mmol), K2CO3 (207 mg, 1.5 mmol) and PdCl2(PPh3)2 (37 mg, 0.05 mmol) were dissolved in a mixture of toluene-MeOH (17 mL:1.7 mL) and heated at 75° C. for 3 hours. The mixture was filtered through celite washed with water and the solvent was evaporated in vacuo. The formed crude residue was acidified with 2 M HCl and extracted into EtOAc and dried over anhyd. Na2SO4, evaporated solvent in vacuo to obtain crude 3′-borono-4-chlorobiphenyl-3-carboxylic acid as a reddish brown solid. The crude product was used for the next step without further purification.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][CH2:11][C:12]([O:14]C)=O)[CH3:9])=[CH:4][CH:3]=1.[CH2:16]([N:18]=[C:19]=[O:20])[CH3:17].FC(F)(F)C(O)=O>C(Cl)Cl.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([N:10]2[CH2:11][C:12](=[O:14])[N:18]([CH2:16][CH3:17])[C:19]2=[O:20])[CH3:9])=[CH:6][CH:7]=1
Reactant: COC(=O)CN[C@H](C)c1ccc(Br)cc1
Reactant: CCN=C=O
Solvent: ClCCl
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: CCN1C(=O)CN([C@H](C)c2ccc(Br)cc2)C1=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
(R)-Methyl 2-(1-(4-bromophenyl)ethylamino)acetate (6G3) (0.845 mmol, 230 mg) was dissolved in DCM (10 ml) and ethyl isocyanate (6C4) (1.690 mmol, 120 mg) added. The mixture was stirred at room temperature for 3 hours, then concentrated and re-dissolved in DCM (5 ml) and trifluoroacetic acid (0.845 mmol, 96 mg) added. Stirring was continued for 1 h and the reaction diluted with DCM (15 ml) and water (20 ml) and the organic phase separated using a hydrophobic fritted tube. Concentration afforded (R)-1-(1-(4-bromophenyl)ethyl)-3-ethylimidazolidine-2,4-dione (6G4) which was used without further purification; 1H NMR (400 MHz, CDCl3) δ 7.50 (d, 2H) 7.18 (d, 2H) 5.43 (q, 1H) 3.76 (d, 1H) 3.56 (q, 2H) 3.46 (d, 1H) 1.57 (d, 3H) 1.22 (t, 3H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5](=O)[CH2:6][C:7]([O:9][CH3:10])=[O:8].[C:13]([CH2:15]C(O)=O)#[N:14].C(O)(=O)C>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5](=[CH:15][C:13]#[N:14])[CH2:6][C:7]([O:9][CH3:10])=[O:8]
Reactant: COC(=O)CC(=O)CC(=O)OC
Reactant: N#CCC(=O)O
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: COC(=O)CC(=CC#N)CC(=O)OC
Temperature: 25 °C
Yield: 68.1 %

Procedure:
To a solution of 3-oxo-pentanedioic acid dimethyl ester (523 g) in toluene (750 mL), cyanoacetic acid (511 g), NH4OAc (46.3 g) and acetic acid (90.1 g) were added and heated at reflux with dehydrating by Dean-Stark apparatus for 8 h. After cooling to room temperature, the reaction mixture was washed with water, saturated aqueous NaHCO3 solution and brine. The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure to give crude 3-cyanomethylene-pentanedioic acid dimethyl ester (403 g) as an oil. 1H NMR (200 MHz, CDCl3) δ ppm 3.39 (d, J=0.88 Hz, 2 H), 3.62 (s, 2 H), 3.72 (s, 3 H), 3.74 (s, 3 H), 5.51 (s, 1 H).
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:14])[C:5]1[CH:10]=[C:9]([S:11][CH3:12])[CH:8]=[C:7]([NH2:13])[CH:6]=1.N1C=CC=CC=1.[Cl:21][CH2:22][CH2:23][CH2:24][S:25](Cl)(=[O:27])=[O:26]>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH3:2][O:3][C:4](=[O:14])[C:5]1[CH:10]=[C:9]([S:11][CH3:12])[CH:8]=[C:7]([NH:13][S:25]([CH2:24][CH2:23][CH2:22][Cl:21])(=[O:27])=[O:26])[CH:6]=1
Reactant: O=S(=O)(Cl)CCCCl
Reactant: COC(=O)c1cc(N)cc(SC)c1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: COC(=O)c1cc(NS(=O)(=O)CCCCl)cc(SC)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 104.3 %

Procedure:
To a solution of 3-amino-5-methylsulfanyl-benzoic acid methyl ester hydrochloride (D62) (130 mg, 0.556 mmol, 1 equiv) in CH2Cl2 (2 ml) was added pyridine (142 ml, 1.75 mmol, 3 equiv), DMAP (6.8 mg, 0.056 mmol, 0.1 equiv) and then 3-chloropropane sulfonyl chloride (71 μl, 0.584 mmol, 1.05 equiv) dropwise over 2 min. The resulting mixture was stirred at room temperature for 2 h, diluted with AcOEt, washed sequentially with 2N aqueous HCl solution, saturated aqueous NaHCO3 solution and brine, dried over Na2SO4 and concentrated in vacuo to give 3-(3-chloropropane-1-sulfonylamino)-5-methylsulfanyl-benzoic acid methyl ester (D66) (196 mg, 104%) as light brown crystals. [M−H]−=336.0 RT=3.20 min
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[C:3]=1[C:20]([O:22][CH2:23][CH3:24])=[O:21].[C:25]1([O:35][CH2:36][CH2:37][OH:38])[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:2]([O:38][CH2:37][CH2:36][O:35][C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=[CH:27][CH:26]=3)=[C:3]2[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:13][CH:14]=1
Reactant: CCOC(=O)c1c(Br)c2ccccc2n1Cc1ccc(OC)cc1
Reactant: OCCOc1cccc2ccccc12
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: CCOC(=O)c1c(OCCOc2cccc3ccccc23)c2ccccc2n1Cc1ccc(OC)cc1
Temperature: 25 °C

Procedure:
To a solution of EXAMPLE 101B (388 mg) and 2-(naphthalen-1-yloxy)ethanol (188 mg) in toluene (3 ml) was added 1,1c-binaphthyl-2-yldi-tert-butylphosphine (7.5 mg), palladium(II) acetate (5 mg) and Cs2CO3 (488 mg). The mixture was purged with argon and stirred at room temperature and then heated at 80° C. overnight. After this time the mixture was diluted with ethyl acetate (200 mL) and washed with water, brine and dried over Na2SO4. After concentration of the solvent, the residue was loaded on a silica gel column and eluted with 5% ethyl acetate in hexane to give EXAMPLE 101C.
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[CH2:11]([C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1)[CH3:12]>>[CH2:11]([C:13]1[CH:18]=[CH:17][C:16]([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[CH:7][NH:8]3)=[CH:4][CH:3]=2)=[CH:15][CH:14]=1)[CH3:12]
Reactant: Brc1ccc2cc[nH]c2c1
Reactant: CCc1ccc(B(O)O)cc1
Product: CCc1ccc(-c2ccc3cc[nH]c3c2)cc1

Procedure:
Prepared by Procedure I and Scheme T using 6-bromo-1H-indole and 4-ethylphenylboronic acid: ESMS m/e: 221.9 (M+H)+.
Reaction SMILES: CC1(C)[O:6][CH:5]([C:7]2[CH:8]=[CH:9][C:10]3[C:16]4=[N:17][O:18][C:19]([C:20]5[O:24][N:23]=[C:22]([C:25]6[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=6)[C:21]=5[C:31]([F:34])([F:33])[F:32])=[C:15]4[CH2:14][O:13][C:11]=3[CH:12]=2)[CH2:4][O:3]1.C(O)(C(F)(F)F)=O>>[C:25]1([C:22]2[C:21]([C:31]([F:34])([F:33])[F:32])=[C:20]([C:19]3[O:18][N:17]=[C:16]4[C:10]5[CH:9]=[CH:8][C:7]([CH:5]([OH:6])[CH2:4][OH:3])=[CH:12][C:11]=5[O:13][CH2:14][C:15]=34)[O:24][N:23]=2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: CC1(C)OCC(c2ccc3c(c2)OCc2c-3noc2-c2onc(-c3ccccc3)c2C(F)(F)F)O1
Solvent: O=C(O)C(F)(F)F
Product: OCC(O)c1ccc2c(c1)OCc1c-2noc1-c1onc(-c2ccccc2)c1C(F)(F)F
Reaction time: 0.75 h
Yield: 101.1 %

Procedure:
A solution of 7-(2,2-dimethyl-1,3-dioxolan-4-yl)-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4H-chromeno[4,3-c]isoxazole (Preparation 61B, 0.042 g, 0.087 mmol) in TFA (1.00 ml, 13.0 mmol) was left standing at room temperature for 45 min. The TFA was removed under reduced pressure, and the residue was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded 1-(3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4H-chromeno[4,3-c]isoxazol-7-yl)ethane-1,2-diol (0.039 g, 0.088 mmol, 100% yield) as an off-white solid. The product had an HPLC ret. time=3.00 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=444.9.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16]#[N:17])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH2:18]([S-:30])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].[Na+]>C(S)CCCCCCCCCCC>[CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16]([S:30][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[NH:17])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: CCCCCCCCCCCC[S-]
Reactant: N#CN1Cc2ccccc2-c2ccccc2C1
Agent: CCCCCCCCCCCCS
Agent: [Na+]
Product: CCCCCCCCCCCCSC(=N)N1Cc2ccccc2-c2ccccc2C1

Procedure:
starting from 5,7-dihydro-6H-dibenz[c,e]azepine-6-carbonitrile and sodium dodecanethiolate in 1-dodecanethiol there is obtained dodecyl 5,7-dihydro-6H-dibenz[c,e]azepine-6-thiocarboximidate, which is purified by flash chromatography on silica gel using n-hexane/ethyl acetate (1:1) as the eluent; 1H-NMR(CDCl3): 0.88 (t, CH3), 1.2-2.0 (20H), 2.5 (t, SCH2), 4.43 (s, 4H), 7.3-7.7 (8H);
Reaction SMILES: [C:1]1([S:7]([N:10]2[CH2:12][CH:11]2[C:13]([N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:22]=3[CH3:28])[CH2:17][CH2:16]2)=[O:14])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[I-].[Na+].[CH2:31]([N:33]=[C:34]=[O:35])[CH3:32]>>[C:1]1([S:7]([N:10]2[CH2:12][CH:11]([C:13]([N:15]3[CH2:16][CH2:17][N:18]([C:21]4[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:22]=4[CH3:28])[CH2:19][CH2:20]3)=[O:14])[N:33]([CH2:31][CH3:32])[C:34]2=[O:35])(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCN=C=O
Reactant: Cc1ccc(C)c(N2CCN(C(=O)C3CN3S(=O)(=O)c3ccccc3)CC2)c1
Agent: [I-]
Agent: [Na+]
Product: CCN1C(=O)N(S(=O)(=O)c2ccccc2)CC1C(=O)N1CCN(c2cc(C)ccc2C)CC1

Procedure:
In analogy to example 2, (RS)-(1-benzenesulfonyl-aziridin-2-yl)-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-methanone (example 2, step 3) was reacted with sodium iodide and ethyl isocyanate to give the title compound as a colorless solid. MS: 471.1 ([M+H]+)
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH:11]=[O:12])=[N:5][CH:6]=[C:7]([O:9][CH3:10])[N:8]=1.[BH4-].[Na+]>CO>[CH3:1][O:2][C:3]1[C:4]([CH2:11][OH:12])=[N:5][CH:6]=[C:7]([O:9][CH3:10])[N:8]=1
Reactant: COc1cnc(C=O)c(OC)n1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1cnc(CO)c(OC)n1
Reaction time: 0.5 h
Yield: 97.7 %

Procedure:
To a solution of 3,5-dimethoxy-pyrazine-2-carbaldehyde (120 mg, 0.71 mmol) in MeOH (8 mL) is added sodium borohydride (40 mg, 1.1 mmol) at 0° C. After the mixture is stirred at this temperature for 0.5 hour, the reaction is quenched with saturated NH4Cl (0.7 mL) and solvent removed in vacuo until dryness. DCM (20 mL) is added, and the solution is dried and solvent removed to give 118 mg of (3,5-dimethoxy-pyrazin-2-yl)-methanol as an oil.
Reaction SMILES: [OH:1]/[N:2]=[CH:3]/[C@H:4]1[CH2:9][CH2:8][C@:7]2([OH:24])[C@H:10]3[C@H:20]([CH2:21][CH2:22][C@:5]12[CH3:6])[C@:18]1([CH3:19])[C@@H:13]([CH2:14][C@@H:15]([OH:23])[CH2:16][CH2:17]1)[CH2:12][CH2:11]3.Cl.[BH3-]C#N.[Na+].[OH-].[Na+]>CO>[OH:1][NH:2][CH2:3][C@H:4]1[CH2:9][CH2:8][C@:7]2([OH:24])[C@H:10]3[C@H:20]([CH2:21][CH2:22][C@:5]12[CH3:6])[C@:18]1([CH3:19])[C@@H:13]([CH2:14][C@@H:15]([OH:23])[CH2:16][CH2:17]1)[CH2:12][CH2:11]3
Reactant: C[C@]12CC[C@H](O)C[C@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](/C=N/O)CC[C@]12O
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: C[C@]12CC[C@H](O)C[C@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](CNO)CC[C@]12O
Reaction time: 6 h
Yield: 74.6 %

Procedure:
A stirred solution of 0.60 g of (E)-17β-hydroxyiminomethyl-5β-androstane-3β,14β-diol (prepared following the procedure described in DE 4,227,605 for similar compounds) in 6 ml of methanol was acidified to pH 3 with 1N HCl. 0.30 g of NaBH3CN were added and 0.1N HCl was continuously added, by means of a pH-stat, to maintain pH 2.8+3.0. After 6 hr, 0.15 g of NaBH3CN were added and the reaction was left on stirring overnight. The solution was basified to pH 10 with 2.5N NaOH and methanol was evaporated under reduced pressure. The mixture was extracted with ethyl acetate; the organic layer was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue was purified by flash-chromatography (SiO2) using cyclohexane/ethyl acetate 20/80 as the eluant; the fractions containing the title compound were collected and evaporated to dryness under reduced pressure. The residue was dissolved with diethyl ether/ethyl acetate and the solution was added with the stoichiometric amount of oxalic acid to give 0.45 g of the title compound (I-ah), as a white solid, oxalate.
Reaction SMILES: C([Li])CCC.[C:6](#[N:8])[CH3:7].[C:9]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.Cl>CCCCCC.O1CCCC1>[OH:16][C:9]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:7][C:6]#[N:8]
Reactant: O=C(c1ccccc1)c1ccccc1
Reactant: CC#N
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: N#CCC(O)(c1ccccc1)c1ccccc1
Temperature: -70 °C

Procedure:
The starting material is prepared as follows: The solution of 650 ml of molar n-butyl lithium in hexane is diluted with 650 ml of dry tetrahydrofuran and the mixture stirred and cooled to -70° C. under a nitrogen atmosphere. Then the solution of 37.2g of acetonitrile in 800 ml of tetrahydrofuran is added steadily over a period of 15 minutes. The resulting suspension is stirred at -70° C. for 1 hour before the solution of 165 g of benzophenone in 800 ml of tetrahydrofuran is added steadily over 15 minutes. When addition is complete, the mixture is stirred without external cooling for 20 minutes, and then poured onto a mixture of 1.5 kg of crushed ice and 200 ml of 6N hydrochloric acid. The organic layer is separated and the aqueous solution extracted with diethyl ether. The combined organic solutions are dried and evaporated to give the β-hydroxy-β,β-diphenyl-propionitrile melting at 135°-8°.
Reaction SMILES: Cl.[F:2][C:3]([F:35])([F:34])[C:4]1[CH:5]=[C:6]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:7][O:8][CH2:9][CH:10]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:11][NH:12][C:13]([CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)=[O:14].Br[CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[F:35][C:3]([F:34])([F:2])[C:4]1[CH:5]=[C:6]([CH:27]=[C:28]([C:30]([F:32])([F:33])[F:31])[CH:29]=1)[CH2:7][O:8][CH2:9][CH:10]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[CH2:11][NH:12][C:13]([CH:15]1[CH2:20][CH2:19][N:18]([CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:17][CH2:16]1)=[O:14]
Reactant: O=C(NCC(COCc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccccc1)C1CCNCC1
Reactant: CC(C)(C)OC(=O)CBr
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)CN1CCC(C(=O)NCC(COCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 20 h
Yield: 92.7 %

Procedure:
A mixture of Compound 4 produced in Example 32 (1.26 g, 2.4 mmol), tert-butyl bromoacetate (0.38 mL, 2.6 mmol), potassium carbonate (1.00 g, 7.2 mmol) and DMF (10 mL) was stirred for 20 hours at room temperature. Water was added to the reaction mixture followed by extracting with ethyl acetate. The organic layers were combined, washed with water and a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was evaporated therefrom in vacuo to give Compound 79 (1.34 g, 93%).
Reaction SMILES: S([O-])([O-])=O.[Na+].[Na+].S(O)(O)(=O)=O.[S:12]([NH:16][CH2:17][CH2:18][NH:19][C:20]1[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=1)([CH3:15])(=[O:14])=[O:13].[C:27](OC(=O)C)(=[O:29])[CH3:28]>O>[C:27]([NH:26][C:23]1[CH:24]=[CH:25][C:20]([NH:19][CH2:18][CH2:17][NH:16][S:12]([CH3:15])(=[O:13])=[O:14])=[CH:21][CH:22]=1)(=[O:29])[CH3:28]
Reactant: CC(=O)OC(C)=O
Reactant: CS(=O)(=O)NCCNc1ccc(N)cc1
Agent: O=S(=O)(O)O
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: O
Product: CC(=O)Nc1ccc(NCCNS(C)(=O)=O)cc1
Reaction time: 1 h

Procedure:
0.2 mol (25.2 g) of sodium sulphite is added, at ambient temperature, to a solution of 0.1 mol (32.7 g) of N-(β-mesylaminoethyl)-para-phenylenediamine sulphate in 150 ml of water, and 0.13 mol (13.17 g) of acetic anhydride is added gradually, whilst stirring. When the addition is complete, stirring is continued for one hour and the expected acetylated derivative which has precipitated in crystalline form is then filtered off. The product is drained, washed with water and dried in vacuo. After recrystallisation from alcohol and drying in vacuo, it melts at 130° C.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[CH3:14][S:15]([O-:17])=[O:16].[Na+]>CS(C)=O.O>[CH3:14][S:15]([C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11])(=[O:17])=[O:16]
Reactant: N#Cc1ccc(F)c(C(F)(F)F)c1
Reactant: CS(=O)[O-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CS(=O)(=O)c1ccc(C#N)cc1C(F)(F)F
Temperature: 80 °C
Reaction time: 22 h

Procedure:
4-Fluoro-3-(trifluoromethyl)benzonitrile (400 mg, 2.12 mmol) was suspended together with sodium methanesulfinate (216 mg, 2.12 mmol) in DMSO (2 ml) and stirred at 80° C. for 22 hours. The reaction was then cooled, diluted with 25 ml H2O and filtered. Filtered solids were evaporated from toluene to give 536 mg of the title substance (quant).
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.F[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21]>>[N+:20]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][CH:12]=1)([O-:22])=[O:21]
Reactant: O=[N+]([O-])c1ccccc1F
Reactant: CCOC(=O)c1ccc(N)cc1
Product: CCOC(=O)c1ccc(Nc2ccccc2[N+](=O)[O-])cc1
Temperature: 160 °C

Procedure:
A mixture of ethyl 4-aminobenzoate (1.00 g, 6.05 mmol) and 2-fluoronitrobenzene (0.64 mL, 6.05 mmol) was heated at 160° C. for 18 h. The crude product was purified by silica gel chromatography, eluting with hexane:EtOAc-70:30, to give the title compound. MS: m/z=287 (M+1).