Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:4][C:5](=O)[CH2:6][N:7]1[C:11]2[C:12]([CH:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=2[N:9]=[C:8]1[NH:22][C:23]1[C:28]([CH3:29])=[CH:27][C:26]([Cl:30])=[CH:25][C:24]=1[O:31][CH3:32])(C)C.[BH4-].[Li+]>O1CCCC1.O>[Cl:16][C:15]1[C:10]2[N:9]=[C:8]([NH:22][C:23]3[C:28]([CH3:29])=[CH:27][C:26]([Cl:30])=[CH:25][C:24]=3[O:31][CH3:32])[N:7]([CH2:6][CH2:5][OH:4])[C:11]=2[C:12]([CH:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[CH:13][CH:14]=1
Reactant: CCC(CC)c1ccc(Cl)c2nc(Nc3c(C)cc(Cl)cc3OC)n(CC(=O)OC(C)C)c12
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CCC(CC)c1ccc(Cl)c2nc(Nc3c(C)cc(Cl)cc3OC)n(CCO)c12
Yield: 62.3 %

Procedure:
To a solution of isopropyl[4-chloro-2-[(4-chloro-2-methoxy-6-methylphenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]acetate (453 mg, 0.920 mmol) in tetrahydrofuran (5 mL) was added lithium tetrahydroborate (60 mg, 2.76 mmol), and the mixture was refluxed for 2 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate (X2). The combined organic layer was washed with brine (X1), dried over sodium sulfate and concentrated in vacuo. The residual solid was recrystallized with ethyl acetate-n-hexane to give 250 mg (0.573 mmol, 62.3%) of the title compound as a colorless crystal. The filtrate was concentrated in vacuo, and the residual solid was recrystallized with ethyl acetate-hexane to give 91 mg (0.209 mmol, 22.7%) of the title compound as a colorless crystal.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:22][CH2:23][CH3:24])=[C:16]([N+:19]([O-])=O)[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:25]#[N:26])[CH:5]=[CH:6][CH:7]=1.[Cl-].[NH4+].CO>O.C(OCC)(=O)C.[Fe]>[NH2:19][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][C:15]=1[O:22][CH2:23][CH3:24])[N:12]=[CH:11][C:10]([C:25]#[N:26])=[C:9]2[NH:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=1
Reactant: CCOc1cc2ncc(C#N)c(Nc3cccc(Br)c3)c2cc1[N+](=O)[O-]
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CO
Solvent: CCOC(C)=O
Product: CCOc1cc2ncc(C#N)c(Nc3cccc(Br)c3)c2cc1N

Procedure:
A mixture of 2.5 g (6 mmol) of 4-[(3-bromophenyl)amino]-7-ethoxy-6-nitro-quinoline-3-carbonitrile, 2.4 g (45 mmol) of ammonium chloride, and 1.5 g (27 mmol) iron was stirred at reflux in 40 ml of water and 40 ml of methanol for 4 hours. The mixture was diluted with 500 ml of hot ethyl acetate and the hot mixture was filtered. The filtration was washed with saturated sodium chloride solution and then the organic layer was dried over sodium sulfate. The solution was concentrated and 1.5 of beige solid was collected: mass spectrum (electrospray, m/e): M+H 382.8 and 384.8.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH:7]=[CH:8][C:9]2[CH:19]=[CH:18][C:12]([C:13](OCC)=[O:14])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH:7]=[CH:8][C:9]2[CH:10]=[CH:11][C:12]([CH2:13][OH:14])=[CH:18][CH:19]=2)=[CH:5][CH:4]=1
Reactant: CCOC(=O)c1ccc(C=Cc2ccc(OC)cc2)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(C=Cc2ccc(CO)cc2)cc1
Reaction time: 1 h

Procedure:
Ethyl 4-(4-methoxystyryl)benzoate (67 g.) in 600 ml. of tetrahydrofuran was gradually added to a suspension of 12 g. of lithium aluminum hydride in 300 ml. of tetrahydrofuran at such a rate to maintain gentle reflux. The reaction mixture was heated at reflux for two hours, then cooled and 24 ml. of water in 24 ml. of tetrahydrofuran added slowly. The mixture was stirred for one hour, heated to reflux temperature and filtered hot through a steam-jacketed funnel. The solvent was removed from the filtrate to give 55 g. of 4-(4-methoxystyryl)benzyl alcohol, m.p. 200°-202° C. when recrystallized from ethanol.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([O:12][CH3:13])[C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].Br[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:11]=[C:10]([O:12][CH3:13])[C:9]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]
Reactant: Brc1ccccn1
Reactant: COC(=O)c1cc(B2OC(C)(C)C(C)(C)O2)c(OC)cc1Cl
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: COC(=O)c1cc(-c2ccccn2)c(OC)cc1Cl
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 35 %

Procedure:
To a solution of methyl 2-chloro-4-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate in dioxane (Preparation 47, 935 mg, 2.86 mmol) was added 2M Na2CO3 (4.30 mL, 8.58 mmol) and stirred for 15 minutes at room temperature. 2-bromopyridine (542 mg, 3.43 mmol) was added and the reaction was purged with nitrogen for 15 minutes. Pd(dppf)Cl2 (117 mg, 0.14 mmol) was added and the reaction heated at 110° C. for 2 hours. The reaction was cooled to room temperature, filtered through arbocel and washed with EtOAc (50 mL). The filtrate was washed with brine (50 mL) and the aqueous layer was re-extracted with EtOAc (50 mL). The combined organic layers were dried over magnesium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 10-20% EtOAc in heptanes to afford the title compound (282 mg, 35% over 2 steps).
Reaction SMILES: [S:1]([O:8]S(C(F)(F)F)(=O)=O)([C:4]([F:7])([F:6])[F:5])(=[O:3])=[O:2].O[C:17]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:18]=1[CH2:19][CH2:20][C:21]2=[O:26].CCN(CC)CC>C(Cl)Cl>[F:5][C:4]([F:7])([F:6])[S:1]([O:8][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:18]=1[CH2:19][CH2:20][C:21]2=[O:26])(=[O:3])=[O:2]
Reactant: O=C1CCc2c(O)cccc21
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C1CCc2c(OS(=O)(=O)C(F)(F)F)cccc21
Temperature: 25 °C
Yield: 67 %

Procedure:
Triflic anhydride (152 g, 0.54 mol) was added dropwise to solution 80 g of compound 86 and 60 g of NEt3 in 1 L CH2Cl2 at 0° C. The resulting mixture was refluxed for 2 h, cooled to room temperature, filtered, washed with water (0.5 L), aqueous citric acid (50 g/0.5 L), brine (0.5 L), dried on Na2SO4, and evaporated to give about 100 g (67%) of compound 87 as dark liquid.
Reaction SMILES: [C:1]([OH:12])(=O)/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH:13]1([SH:18])[CH2:17][CH2:16][CH2:15][CH2:14]1>>[C:1](=[O:12])([S:18][CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: SC1CCCC1
Reactant: CCCCCCC/C=C/C(=O)O
Product: CCCCCCC/C=C/C(=O)SC1CCCC1

Procedure:
The same operation as in Example 1-1 or 1-2 was carried out using trans-2-decenoic acid and cyclopentanethiol as starting materials to give the aimed compound.
Reaction SMILES: C(S(C[C@@H](CC1C=CC=CC=1)C(N[C@H:13]([C:32]([OH:34])=O)[CH2:14][C:15]1[N:19]=[CH:18][N:17]([C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][C:21]=2[N+:29]([O-:31])=[O:30])[CH:16]=1)=O)(=O)=O)(C)(C)C.[NH2:42][C@@H:43]([CH2:51][CH:52]1[CH2:57][CH2:56][CH2:55][CH2:54][CH2:53]1)[C@@H:44]([OH:50])[C:45]([CH:47]1[CH2:49][CH2:48]1)=[O:46]>>[CH:52]1([CH2:51][C@H:43]([NH:42][C:32](=[O:34])[CH2:13][CH2:14][C:15]2[N:19]=[CH:18][N:17]([C:20]3[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][C:21]=3[N+:29]([O-:31])=[O:30])[CH:16]=2)[C@@H:44]([OH:50])[C:45]([CH:47]2[CH2:48][CH2:49]2)=[O:46])[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57]1
Reactant: N[C@@H](CC1CCCCC1)[C@@H](O)C(=O)C1CC1
Reactant: CC(C)(C)S(=O)(=O)C[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1cn(-c2ccc([N+](=O)[O-])cc2[N+](=O)[O-])cn1)C(=O)O
Product: O=C(CCc1cn(-c2ccc([N+](=O)[O-])cc2[N+](=O)[O-])cn1)N[C@@H](CC1CCCCC1)[C@@H](O)C(=O)C1CC1

Procedure:
In an analogous manner to that described in Example 23, by condensing N-[(S)-α-[(tert-butylsulphonyl)methyl]hydrocinnamoyl]-1-(2,4-dinitrophenyl)-L-histidine and (2R,3S)-3-amino-4-cyclohexyl-1-cyclopropyl-2-hydroxy-1-butanone there is obtained (S)-α-[(S)-α-(tert-butylsulphonyl)methyl]hydrocinnamamido]-N-[(1S,2R)-1-(cyclohexylmethyl)-3-cyclopropyl-2-hydroxy-3-oxopropyl]-1-(2,4-dinitrophenyl)imidazole-4-propionamide as a yellow solid, MS: 795 (M+H)+.
Reaction SMILES: [OH-:1].[Na+].C[O:4][C:5](=[O:51])[C@H:6]([O:20][C:21]1[C:26]([Br:27])=[CH:25][C:24]([C:28]2[CH:33]=[CH:32][C:31]([C:34]3[C:35]4[CH:49]=[CH:48][CH:47]=[CH:46][C:36]=4[S:37][C:38]=3[CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[CH:30][CH:29]=2)=[CH:23][C:22]=1[Br:50])[CH2:7][CH2:8][N:9]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]1=[O:19].CO.Cl>O.O1CCCC1>[CH2:39]([C:38]1[S:37][C:36]2[CH:46]=[CH:47][CH:48]=[CH:49][C:35]=2[C:34]=1[C:31]1[CH:32]=[CH:33][C:28]([C:24]2[CH:23]=[C:22]([Br:50])[C:21]([O:20][C@@H:6]([C:5]([OH:4])=[O:51])[CH2:7][CH2:8][NH:9][C:10](=[O:19])[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:17]([OH:1])=[O:18])=[C:26]([Br:27])[CH:25]=2)=[CH:29][CH:30]=1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1
Reactant: [OH-]
Reactant: COC(=O)[C@@H](CCN1C(=O)c2ccccc2C1=O)Oc1c(Br)cc(-c2ccc(-c3c(Cc4ccccc4)sc4ccccc34)cc2)cc1Br
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1ccccc1C(=O)NCC[C@@H](Oc1c(Br)cc(-c2ccc(-c3c(Cc4ccccc4)sc4ccccc34)cc2)cc1Br)C(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 74 %

Procedure:
Sodium hydroxide (2 N, 5.0 mL) was added into a mixture of (2R)-2-[4′-(2-benzyl-benzo[b]-thiophen-3-yl)-3,5-dibromo-biphenyl-4-yloxy]-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyric acid methyl ester (1.0 g, 1.26 mmol), methyl alcohol (10 ml) and tetrahydrofuran (10 mL). The reaction mixture was stirred at room temperature for 1 hour, poured into water, acidified with HCl (2 N), and extracted with ethyl ether. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography on acidic silica gel (hexanes/EtAOc 2:1) gave white solid (0.82 g, 74% yield): mp 130-132° C.; MS m/e 797 (M+);
Reaction SMILES: [C:1]([O:5][C:6](=[O:32])[CH2:7][CH:8]([C:18]1[CH:23]=[CH:22][C:21]([NH:24]C(OC(C)(C)C)=O)=[CH:20][CH:19]=1)[NH:9][C:10]([C:12]1[CH:16]=[C:15]([CH3:17])[O:14][N:13]=1)=[O:11])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>ClCCl>[C:1]([O:5][C:6](=[O:32])[CH2:7][CH:8]([C:18]1[CH:19]=[CH:20][C:21]([NH2:24])=[CH:22][CH:23]=1)[NH:9][C:10]([C:12]1[CH:16]=[C:15]([CH3:17])[O:14][N:13]=1)=[O:11])([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1cc(C(=O)NC(CC(=O)OC(C)(C)C)c2ccc(NC(=O)OC(C)(C)C)cc2)no1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(C(=O)NC(CC(=O)OC(C)(C)C)c2ccc(N)cc2)no1
Reaction time: 4 h
Yield: 64.5 %

Procedure:
A solution of (R) 3-(4-tert-butoxycarbonylamino-phenyl)-3-[(5-methyl-isoxazole-3-carbonyl)-amino]-propionic acid tert-butyl ester (2 g, Reference Example 11) in dichloromethane (50 mL) was treated with trifluoroacetic acid (5 mL). After four hours [the reaction was monitored by TLC: no more starting material was visible after about 4 hours] at room temperature the reaction mixture was poured carefully onto a mixture of sodium hydrogen carbonate solution (100 mL, 5% w/v) and dichloromethane (50 mL). The organic layer was separated then dried and then evaporated to give the title compound (1.0 g) as a yellow oil which slowly crystallised on standing.
Reaction SMILES: [OH-].[Na+].[C:3]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][CH:10]([CH2:14][CH3:15])[C:11](O)=[O:12].S(Cl)([Cl:24])=O>>[C:3]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][CH:10]([CH2:14][CH3:15])[C:11]([Cl:24])=[O:12]
Reactant: O=S(Cl)Cl
Reactant: CCC(Cc1ccccc1-c1ccccc1)C(=O)O
Agent: [Na+]
Agent: [OH-]
Product: CCC(Cc1ccccc1-c1ccccc1)C(=O)Cl
Yield: 106.3 %

Procedure:
To a 100-ml three-necked round flask (equipped with a stirrer tip, a Dimroth condenser, a thermometer and a trap of NaOH) were introduced 13.3 g (52.4 mmol) of 3-(2-biphenylyl)-2-ethylpropionic acid and 25.9 ml (355 mmol) of thionyl chloride, and they were refluxed for 2.5 hours with heating in a nitrogen atmosphere. After the reaction was completed, the unreacted thionyl chloride was distilled off under reduced pressure to obtain 15.2 g of a crude product as a yellow orange liquid. This acid chloride was used for the next reaction without further purification. The properties of the product thus obtained are described below.
Reaction SMILES: C(N(CC)CC)C.[OH:8][CH:9]1[CH2:14][C:13]([CH3:16])([CH3:15])[NH+:12]([O-:17])[C:11]([CH3:19])([CH3:18])[CH2:10]1.[C:20](OC(=O)C)(=[O:22])[CH3:21]>O1CCCC1>[C:20]([O:8][CH:9]1[CH2:14][C:13]([CH3:15])([CH3:16])[NH+:12]([O-:17])[C:11]([CH3:19])([CH3:18])[CH2:10]1)(=[O:22])[CH3:21]
Reactant: CC(=O)OC(C)=O
Reactant: CC1(C)CC(O)CC(C)(C)[NH+]1[O-]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(=O)OC1CC(C)(C)[NH+]([O-])C(C)(C)C1
Temperature: 25 °C
Yield: 78.5 %

Procedure:
To a solution in which 30.3 g (300 mmol) of triethylamine and 34.4 g (200 mmol) of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxide (TEMPOL) were dissolved in 200 mL of tetrahydrofuran (THF), 25.5 g (250 mmol) of acetic anhydride was added at 0° C. The temperature was raised to 25° C. to carry out a reaction for 12 hours, and it was then concentrated by a rotary evaporator. The residue was supplied to 1 liter of iced water, and the precipitated orange solid was collected by filtration to obtain 33.8 g of 4-acetyloxy-2,2,6,6-tetramethylpiperidine-N-oxide.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([NH:19][S:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:25][CH:24]=2)(=[O:22])=[O:21])[C:10]([N:12]2[CH2:17][CH2:16][CH:15]([CH3:18])[CH2:14][CH2:13]2)=[O:11])=[CH:4][C:3]=1[N+:35]([O-])=O.[CH:38](O)=O>[Pd]>[NH:1]1[C:2]2[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([NH:19][S:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:10]([N:12]3[CH2:17][CH2:16][CH:15]([CH3:18])[CH2:14][CH2:13]3)=[O:11])=[CH:4][C:3]=2[N:35]=[CH:38]1
Reactant: CC1CCN(C(=O)C(Cc2ccc(N)c([N+](=O)[O-])c2)NS(=O)(=O)c2ccc(-c3ccccc3)cc2)CC1
Reactant: O=CO
Agent: [Pd]
Product: CC1CCN(C(=O)C(Cc2ccc3[nH]cnc3c2)NS(=O)(=O)c2ccc(-c3ccccc3)cc2)CC1

Procedure:
Prepared from N-[1-((4-amino-3-nitro-phenyl)-methyl)-2-(4-methyl-piperidin-1-yl)-2-oxo-ethyl]-4-biphenylylsulphonamide and cyclising with formic acid in the presence of palladium/charcoal analogously to Example 1.
Reaction SMILES: CC(C)C[N:4]1[CH2:8][C:7](=[O:9])[NH:6]C1C(C)C.[OH:14][CH:15]([CH3:20])[CH2:16][C:17]([O-:19])=O.C(O)(=O)C1C=CC=CC=1.O>C(O)CCCC>[OH:14][CH:15]1[CH2:20][N:4]([CH2:8][C:7]([NH2:6])=[O:9])[C:17](=[O:19])[CH2:16]1
Reactant: CC(C)CN1CC(=O)NC1C(C)C
Reactant: CC(O)CC(=O)[O-]
Agent: O=C(O)c1ccccc1
Solvent: O
Solvent: CCCCCO
Product: NC(=O)CN1CC(O)CC1=O
Yield: 62.1 %

Procedure:
A solution of 2-methylpropyl 2-(1-methylethyl)-4-oxoimidazolidine-β-hydroxybutanoate (15 g, 52.4 mmol), benzoic acid (6.4 g, 52.4 mmol) and water (3.75 ml, 208 mmol) in n-pentanol (90 ml) was refluxed under nitrogen for 6 hr. After cooling the mixture was extracted twice with water (35 ml). The aqueous extracts were evaporated to dryness and the residue was crystallized from methanol to give 5.15 g (62.1%) of the title compound, m.p. 167°-70° C.
Reaction SMILES: Br[CH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH2:11][C:10](=[O:13])[NH:9][C:8]=2[CH:14]=1.[I-].[K+].C[N:18](C)C=O>>[NH2:18][CH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH2:11][C:10](=[O:13])[NH:9][C:8]=2[CH:14]=1
Reactant: O=C1COc2ccc(CCBr)cc2N1
Reactant: CN(C)C=O
Agent: [I-]
Agent: [K+]
Product: NCCc1ccc2c(c1)NC(=O)CO2

Procedure:
In a 250-cm3 ground-necked flask, 0.01 mol of 6-(2-bromoethyl)-3-oxo-2,3-dihydro-1,4-benzoxazine and 0.3 g of potassium iodide are dissolved in 30 cm3 of dimethylformamide.
Reaction SMILES: [Cl:1]C(Cl)(Cl)C(Cl)=O.[F:8][C:9]([F:36])([F:35])[C:10]([CH2:25][C:26]1[NH:34][C:33]2[CH:32]=[CH:31][N:30]=[CH:29][C:28]=2[CH:27]=1)([OH:24])[CH2:11][C:12]([C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[O:22][CH3:23])([CH3:14])[CH3:13]>CN(C=O)C>[Cl:1][C:27]1[C:28]2[CH:29]=[N:30][CH:31]=[CH:32][C:33]=2[NH:34][C:26]=1[CH2:25][C:10]([OH:24])([CH2:11][C:12]([C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[O:22][CH3:23])([CH3:14])[CH3:13])[C:9]([F:35])([F:8])[F:36]
Reactant: COc1ccc(F)cc1C(C)(C)CC(O)(Cc1cc2cnccc2[nH]1)C(F)(F)F
Reactant: O=C(Cl)C(Cl)(Cl)Cl
Solvent: CN(C)C=O
Product: COc1ccc(F)cc1C(C)(C)CC(O)(Cc1[nH]c2ccncc2c1Cl)C(F)(F)F
Reaction time: 48 h
Yield: 55.5 %

Procedure:
A solution of trichloroacetyl chloride (0.045 mL, 0.403 mmol) in 0.5 mL of DMF was treated with a solution of 1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-(1H-pyrrolo[3,2-c]pyridin-2-ylmethyl)pentan-2-ol (33.0 mg, 0.081 mmol) in 0.5 mL of DMF at room temperature. After 2 days, the reaction was quenched with 2 mL of ice-water and 2 mL of cold 1 N sodium hydroxide solution. The resulting mixture was extracted with three 5 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Chromatography on SiO2 (100% dichloromethane to 10% methanol in dichloromethane, gradient) gave 20.0 mg of the title product (56% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[NH:7][C:6]([C:12](Cl)=[O:13])=[CH:5]2.N1C=CC=CC=1.[CH:21]1[C:26]([NH2:27])=[CH:25][CH:24]=[C:23]([S:28]([NH:31][C:32]2[S:36][CH:35]=[CH:34][N:33]=2)(=[O:30])=[O:29])[CH:22]=1>C(Cl)Cl>[S:36]1[CH:35]=[CH:34][N:33]=[C:32]1[NH:31][S:28]([C:23]1[CH:22]=[CH:21][C:26]([NH:27][C:12]([C:6]2[NH:7][C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([Cl:1])=[CH:10][C:9]=3[Cl:11])=[O:13])=[CH:25][CH:24]=1)(=[O:30])=[O:29]
Reactant: Nc1ccc(S(=O)(=O)Nc2nccs2)cc1
Reactant: O=C(Cl)c1cc2cc(Cl)cc(Cl)c2[nH]1
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(Nc1ccc(S(=O)(=O)Nc2nccs2)cc1)c1cc2cc(Cl)cc(Cl)c2[nH]1
Temperature: 25 °C
Reaction time: 16 h
Yield: 90 %

Procedure:
To a solution of 5,7-dichloro-indole-2-carbonylchloride (186 mg, 0.75 mmol) in pyridine (0.8 mL, 1 mmol) and DCM (5.2 mL) was added N′-(2-thiazolyl)sulfanilamide (128 mg, 0.5 mmol) and the reaction mixture stirred at rt for 16 h. The resulting solid was filtered, washed with DCM (3×5 mL), and dried under vacuum overnight to provide the product (0.21 g; yield=90%) as a white-green solid. 1H-NMR (DMSO-d6) 12.78 (s, 1H), 12.33 (s, 1H), 10.67 (s, 1H), 7.97 (d, J=7.0 Hz, 2H), 7.82 (d, J=7.0 Hz, 2H), 7.62 (d, J=1.5 Hz, 1H), 7.47 (s, 1H), 7.30 (d, J=1.7 Hz, 1H), 7.27 (d, J=4.6 Hz, 1H), 6.84 (d, J=4.6 Hz, 1H). LC/MS (10-99%) M/Z: M+1 obs=467.0; tR=3.12 min.
Reaction SMILES: [C:1]1([C:7]2[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]=2[OH:21])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][CH:24]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O>[C:1]1([C:7]2[C:16]([C:17]([F:19])([F:20])[F:18])=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]=2[O:21][C:23]2[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][CH:24]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=Cc1ccc(F)cc1
Reactant: Oc1c(-c2ccccc2)c(C(F)(F)F)cc2ccccc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Product: O=Cc1ccc(Oc2c(-c3ccccc3)c(C(F)(F)F)cc3ccccc23)cc1
Yield: 36 %

Procedure:
2-Phenyl-3-(trifluoromethyl)-1-naphthalenol (182) (0.19 g, 0.66 mmol) and 4-fluorobenzaldehyde was heated with Cs2CO3 in DMSO at 100° C. to give 92 mg (36%) of the title compound (183) as alight brown solid. 1H NMR (400 MHz, CDCl3): δ 6.67 (d, J=8.8 Hz, 2H), 7.14 (d, J=6.9 Hz, 2H), 7.18-7.27 (m, 3H), 7.58-7.70 (m, 4H), 7.89 (d, J=8.2 Hz, 1H), 8.05 (d, J=8.1 Hz, 1H), 8.27 (s, 1H), 9.82 (s, 1H). LCMS (ESI): m/z 415 (M+Na)+.
Reaction SMILES: [C:1](O)(=O)[C:2]([CH3:5])([CH3:4])[CH3:3].[NH2:8][CH2:9][CH:10]([OH:13])[CH2:11][NH2:12]>O>[C:2]([C:1]1[NH:8][CH2:9][CH:10]([OH:13])[CH2:11][N:12]=1)([CH3:5])([CH3:4])[CH3:3]
Reactant: CC(C)(C)C(=O)O
Reactant: NCC(O)CN
Solvent: O
Product: CC(C)(C)C1=NCC(O)CN1
Temperature: 0 °C
Yield: 62 %

Procedure:
The feed solution was comprised of 41.4 percent pivalic acid, 43.9 percent 1,3-diamino-2-propanol, and 14.6 percent water, corresponding to a 1/1.2/2 molar ratio, and was kept warm on a hot plate stirrer and pumped through a heated line to the catalyst bed. Pivalic acid (167.4 g, 1.64 mol), 1,3-diamino-2-propanol (177.5 g, 1.97 mol), and water (59.0 g, 3.28 mol) were pumped as a single feed to the alumina bed held at 275° C., at a rate of 1.5 g/min. A preheater tube held at 250° C. served to vaporize the feed components. A nitrogen flow rate of 210 mL/min was applied to the reactor during the run. The reactor effluent was condensed with a hot water condenser to prevent crystallization. The product consisted of an orange oil containing crystalline solid and was stripped on a rotary evaporator to remove water. A roughly equal volume of acetonitrile was added, the slurry cooled to 0° C., and crystalline product was collected on a filter and dried in a vacuum oven at 60° C. to give 139.2 g of 2-t-butyl-5-hydroxy-1,4,5,6-tetrahydropyrimidine as a first crop. The mother liquor was reduced in volume to give an orange oil and placed in an oven at 80° C. overnight. After addition of acetonitrile to the resulting solid and filtration as above, an additional 60.1 g solid was obtained, which was 84 percent pure, most of the remainder being uncyclized materials. The total of 189.7 g of 2-t-butyl-5-hydroxy-1,4,5,6-tetrahydropyrimidine represented a 74 percent isolated yield based on pivalic acid, and a 62 percent yield based on 1,3-diamino-2-propanol. A pure sample was prepared by recrystallization from warm CH3CN: mp 212°-214° C. (corrected, decomp); 1H NMR (D2O/CD3CN) δ 3.9 (m, 1H), 3.1 (apparent dt, 2H), 2.9 (apparent dd, 2H), 1.0 ppm (s, 3H); 13C NMR {1H} (D2O/CD3CN) δ 168.7 (1 C), 60.0 (1 C), 47.0 (2 C), 37.0 (1 C), 27.7 ppm (3 C); Anal. Calcd for C8H16N2O: C, 61.50; H, 10.32; N, 17.93. Found: C, 61.57; H, 10.50; N, 18.01.
Reaction SMILES: C([BH-](C(CC)C)C(CC)C)(CC)C.[Li+].C(O)(=O)C.[OH:19][CH2:20][C@@:21]12[C@@H:38]3[C@H:29]([C@H:30]4[C@@:34]([CH2:36][CH2:37]3)([CH3:35])[C:33](=[O:39])[CH2:32][CH2:31]4)[CH2:28][CH2:27][C@H:26]1[CH2:25][C:24](=[O:40])[CH2:23][CH2:22]2.[OH-].[Na+].OO.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[CH3:35][C@:34]12[CH2:36][CH2:37][C@H:38]3[C@@H:29]([CH2:28][CH2:27][C@@H:26]4[C@:21]3([CH2:20][OH:19])[CH2:22][CH2:23][C@@H:24]([OH:40])[CH2:25]4)[C@@H:30]1[CH2:31][CH2:32][C@@H:33]2[OH:39]
Reactant: C[C@]12CC[C@H]3[C@@H](CC[C@H]4CC(=O)CC[C@@]43CO)[C@@H]1CCC2=O
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: O=C([O-])[O-]
Agent: OO
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: C[C@]12CC[C@H]3[C@@H](CC[C@H]4C[C@H](O)CC[C@@]43CO)[C@@H]1CC[C@@H]2O
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A 1 M solution of lithium tri-sec-butylborohydride in tetrahydrofuran under nitrogen is cooled in a dry ice-acetone bath to -78° C. and 19-hydroxy-5α-androstane-3,17-dione acetate is slowly added. The reaction mixture is stirred for 2 hours at this temperature, warmed to 0° C. and stirring continued for an additional two hours. The reaction mixture is decomposed by the addition of 3 N sodium hydroxide solution followed by a 30% hydrogen peroxide solution. Solid potassium carbonate is added to this mixture and the tetrahydrofuran decanted therefrom. The solid residue is washed with fresh tetrahydrofuran and the combined tetrahydrofuran solutions are dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The residue is crystallized from acetone to yield 5α-androstane-3α,17β,19-triol.