Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC(C)([O-])C.[Na+].O=[C:8]([CH:10]=[C:11]([CH3:13])[CH3:12])[CH3:9].[C:14](OCC)(=O)[C:15]([O:17][CH2:18][CH3:19])=[O:16].[CH3:24][NH:25][NH2:26]>C(O)C.C(O)(=O)C>[CH3:24][N:25]1[C:8]([CH:10]=[C:11]([CH3:13])[CH3:12])=[CH:9][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:26]1
Reactant: CCOC(=O)C(=O)OCC
Reactant: CNN
Reactant: CC(=O)C=C(C)C
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)c1cc(C=C(C)C)n(C)n1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Under a nitrogen atmosphere, sodium tert-butoxide (54.1 g, 0.564 mol) and ethanol (187 mL) were combined at 0° C. The mixture was stirred at ambient temperature for 30 minutes. A mixture of mesityl oxide (30 mL, 0.26 mol) and diethyl oxalate (35.6 mL, 0.26 mol) in ethanol (40 mL) was added over a period of 1 minute. The reaction mixture was stirred for 2.5 hours at ambient temperature and then cooled to 0° C. Acetic acid (131 mL) and methyl hydrazine (15.3 mL, 0.288 mol) were added. The reaction was allowed to warm to ambient temperature with stirring overnight and then concentrated under reduced pressure. The residue was diluted with chloroform (500 mL) and water (1 L) and the mixture was adjusted to pH 11 with the addition of 50% sodium hydroxide. The aqueous layer was extracted with chloroform (3×250 mL); the combined organics were dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide ethyl 1-methyl-5-(2-methylprop-1-enyl)-1H-pyrazole-3-carboxylate as a black oil that was used without purification.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]#[N:7].[N-:8]=[N+:9]=[N-:10].[Na+]>CN(C)C=O.O>[N:8]([CH2:2][CH2:3][CH2:4][CH2:5][C:6]#[N:7])=[N+:9]=[N-:10]
Reactant: N#CCCCCBr
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: N#CCCCCN=[N+]=[N-]
Temperature: 100 °C
Reaction time: 4 h

Procedure:
A solution of 5-bromovaleronitrile (48.6 g, 0.3 mol) in N, N-dimethylformamide (600 ml) was treated with sodium azide (23.4 g, 0.36 mol) and stirred at 100° C. for 4 h. The reaction mixture was cooled to 23° C. and diluted with water (500 ml); the resulting solution was extracted with ether (4×400 ml). The ether extracts were combined, washed with water (3×200 ml) and dried over anhydrous magnesium sulfate. The evaporation of ether under reduced pressure gave a yellow liquid which was distilled under high vacuum; bp 83°-4° C. (0.6 mm)1 ; 1Hmr (CDCl3) δ: 3.37 (2H, m, δ-H), 2.4 (2H, m, α-H) and 2.0-1.3 ppm (4H, β-H and γ-H).
Reaction SMILES: [OH-].[Na+].C[O:4][C:5](=[O:32])[CH2:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:31])[CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:15][CH:14]=2)[CH2:9][CH2:8]1>C1COCC1.CO.O>[C:27]([O:26][C:24]([NH:23][CH2:22][CH2:21][C:20]([NH:19][C:16]1[CH:17]=[CH:18][C:13]([C@H:10]2[CH2:11][CH2:12][C@H:7]([CH2:6][C:5]([OH:32])=[O:4])[CH2:8][CH2:9]2)=[CH:14][CH:15]=1)=[O:31])=[O:25])([CH3:30])([CH3:28])[CH3:29]
Reactant: COC(=O)C[C@H]1CC[C@H](c2ccc(NC(=O)CCNC(=O)OC(C)(C)C)cc2)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: CC(C)(C)OC(=O)NCCC(=O)Nc1ccc([C@H]2CC[C@H](CC(=O)O)CC2)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
NaOH (47.8 mg, 1.19 mmol) was added to trans-{4-[4-(3-tert-butoxycarbonylaminopropionylamino)phenyl]cyclohexyl}acetic acid methyl ester (50 mg, 0.12 mmol) dissolved in THF/MeOH/water (20 mL, 3:2:1). The reaction mixture was stirred at 25° C. for 5 hours and concentrated under vacuum. The residue was acidified with 1M HCl up to pH of 2 and extracted with ethyl acetate. The extract was washed with brine and dried with anhydrous sodium sulfate and concentrated under vacuum. Acetonitrile was added thereto and cooled to obtain a filtrate, and the filtrate was filtered and separated to obtain the desired compound (47 mg, 97%) as a white solid.
Reaction SMILES: [CH2:1]([C@@H:8]1[O:12][C:11]([CH3:14])([CH3:13])[O:10][C@H:9]1[CH2:15][CH2:16][O:17][Si](C(C)(C)C)(C)C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.CCOC(C)=O>[CH2:1]([C@@H:8]1[O:12][C:11]([CH3:14])([CH3:13])[O:10][C@H:9]1[CH2:15][CH2:16][OH:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC1(C)O[C@@H](CCO[Si](C)(C)C(C)(C)C)[C@H](Cc2ccccc2)O1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC1(C)O[C@@H](CCO)[C@H](Cc2ccccc2)O1
Reaction time: 5 h
Yield: 94.2 %

Procedure:
To a stirred solution of (2-((4S,5S)-5-benzyl-2,2-dimethyl-1,3-dioxolan-4-yl)ethoxy)(tert-butyl)dimethylsilane (Preparation example 240, 11.5 g, 32.80 mmol) in THF (115 mL) was slowly added tetrabutylammonium fluoride (TBAF, 1.0M in THF, 48.8 mL, 48.8 mmol) at room temperature. The mixture was stirred for 5 h. The resulting mixture was diluted with EtOAc, washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated. The crude compound was purified by a silica gel column to produce the title compound (7.3 g, 80˜95%)
Reaction SMILES: C[O:2][C:3]([CH2:5][N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][C:8](=[O:16])[C:7]1=[O:17])=O.[NH3:18]>>[C:3]([CH2:5][N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][C:8](=[O:16])[C:7]1=[O:17])(=[O:2])[NH2:18]
Reactant: COC(=O)Cn1c(=O)c(=O)[nH]c2ccccc21
Reactant: N
Product: NC(=O)Cn1c(=O)c(=O)[nH]c2ccccc21
Reaction time: 18 h
Yield: 32 %

Procedure:
A mixture of 0.17 g (0.7 mmol) 1-methoxycarbonylmethylquinoxaline-2,3(1H,4H)-dione and 10 ml 25% aqueous ammonia was stirred for 18 h. The product was filtered off and washed with cold water to give 0.05 g (32%) 1-carbamoylmethylquinoxaline-2,3(1H,4H)-dione. M.p. >300° C. MS m/c: 219 (M+, 40%), 119 (100%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C@H:20]3[C@H:15]([CH2:16][CH:17]=[CH:18][CH2:19]3)[C:14](=[O:21])[N:13]([CH2:22][CH2:23][CH2:24][CH2:25]Br)[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[NH:27]1[CH:31]=[CH:30][N:29]=[CH:28]1.[ClH:32].COC1C=C(C2[C@H]3[C@H](CCCC3)C(=O)N(CCN3C=CN=C3)N=2)C=CC=1OC>>[ClH:32].[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C@H:20]3[C@H:15]([CH2:16][CH:17]=[CH:18][CH2:19]3)[C:14](=[O:21])[N:13]([CH2:22][CH2:23][CH2:24][CH2:25][N:27]3[CH:31]=[CH:30][N:29]=[CH:28]3)[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: c1c[nH]cn1
Reactant: COc1ccc(C2=NN(CCCCBr)C(=O)[C@H]3CC=CC[C@@H]23)cc1OC
Agent: COc1ccc(C2=NN(CCn3ccnc3)C(=O)[C@H]3CCCC[C@@H]23)cc1OC
Agent: Cl
Product: COc1ccc(C2=NN(CCCCn3ccnc3)C(=O)[C@H]3CC=CC[C@@H]23)cc1OC

Procedure:
Prepared from compound 114 and imidazole as described for compound 113. The reaction mixture was evaporated and the residue dissolved in 2N HCl. After extraction with dichloromethane and drying over magnesium sulfate, the solvent was evaporated. The residue crystallized on treating with ethyl acetate. M.p. 192°-194° C.
Reaction SMILES: [C:1]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H].[C:22](O)(=O)[CH3:23]>Cl.[Pd]>[C:2]1([CH2:1][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:22][CH3:23])=[O:18])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [H][H]
Reactant: O=C(O)CCCCCCCCC(=O)c1ccccc1
Reactant: CC(=O)O
Agent: [Pd]
Agent: Cl
Product: CCOC(=O)CCCCCCCCCc1ccccc1

Procedure:
A solution of 26.15 g of 9-benzoylnonanoic acid in 260 ml of glacial acetic acid and 1 ml of 0.1N hydrochloric acid is hydrogenated (normal pressure) at 30°-35° C. with 2.6 g of palladium-on-charcoal (5% by weight) as catalyst. When no more hydrogen is taken up, the mixture is filtered and the filtrate is evaporated under reduced pressure. The residue is dissolved in 200 ml of ethanol and 2 ml of concentrated sulfuric acid and the solution is refluxed for 22 hours. The solvent is evaporated off and the residue is treated with water and extracted with ether. The organic phase is separated off, washed with water, sodium bicarbonate solution (10% by weight) and saturated sodium chloride solution, dried and evaporated. Distillation of the residue under high vacuum (1 mbar, 137°-141° C.) gives 20 g of ethyl 10-phenyldecanoate.
Reaction SMILES: [C:1]([C:3]1[S:4][C:5]2[CH:11]=[C:10]([OH:12])[CH:9]=[CH:8][C:6]=2[N:7]=1)#[N:2].N1C=CN=C1.[C:18]([Si:22]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)Cl)([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C.C(OCC)(=O)C>[C:1]([C:3]1[S:4][C:5]2[CH:11]=[C:10]([O:12][Si:22]([C:18]([CH3:21])([CH3:20])[CH3:19])([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1)#[N:2]
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: N#Cc1nc2ccc(O)cc2s1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](Oc1ccc2nc(C#N)sc2c1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 112 %

Procedure:
A solution of 2-cyano-6-hydroxybenzothiazole (5.0 g, 28 mmol) in 100 ml of anhydrous DMF under inert atmosphere was treated with 2.9 g of imidazole (4.2 mmol) followed by t-butyldiphenylchlorosilane (9.34 g, 34 mmol). The reaction was stirred at room temperature for 3 h and then diluted with 200 ml of ethyl acetate and washed with water (4×400 ml). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography, eluting with 5-10% ethyl acetate/hexanes to afford 13.0 g of the desired product containing ~10% silyl impurity in quantitative yield. The product was taken on without further purification. 1H NMR (CDCl3): δ1.12 (s, 9H); 7.13-7.46 (m, 8H); 7.70-7.72 (m, 4H); 7.92-7.95 (d, 1H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:38])[C@@H:7]([CH:35]([CH3:37])[CH3:36])[N:8]([CH2:30][CH2:31][CH:32]([CH3:34])[CH3:33])[S:9]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17](OS(C(F)(F)F)(=O)=O)[CH:18]=2)[CH:13]=1)(=[O:11])=[O:10])([CH3:4])([CH3:3])[CH3:2].[Cl-].[Li+].[CH3:41][Sn](C)(C)C>CN(C)C=O.C1(P([Pd](Cl)(Cl)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6](=[O:38])[C@@H:7]([CH:35]([CH3:36])[CH3:37])[N:8]([CH2:30][CH2:31][CH:32]([CH3:33])[CH3:34])[S:9]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([CH3:41])[CH:18]=2)[CH:13]=1)(=[O:10])=[O:11])([CH3:3])([CH3:4])[CH3:2]
Reactant: C[Sn](C)(C)C
Reactant: CC(C)CCN([C@@H](C(=O)OC(C)(C)C)C(C)C)S(=O)(=O)c1ccc2cc(OS(=O)(=O)C(F)(F)F)ccc2c1
Agent: Cl[Pd](Cl)([PH](c1ccccc1)(c1ccccc1)c1ccccc1)[PH](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: Cc1ccc2cc(S(=O)(=O)N(CCC(C)C)[C@@H](C(=O)OC(C)(C)C)C(C)C)ccc2c1
Temperature: 80 °C
Yield: 48.5 %

Procedure:
To a solution of N-isoamyl-N-(6-trifluoromethanesulfonyloxy naphthalene-2-sulfonyl)-D-valine tert-butyl ester (1.1 g, 1.89 mmol) in N,N-dimethylformamide (20 mL) is added lithium chloride (0.40 g, 9.5 mmol), tetramethyl tin (0.525 mL, 3.79 mmol), and bistriphenylphosphino palladium dichloride (0.066 g, 0.095 mmol). The reaction is heated to 80° C. for 16 h. The reaction is allowed to cool to ambient temperature and filtered through Celite. The filtrate is poured over water and extracted three times with dichloromethane. The combined organic extracts were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue is purified by column chromatography (4% hexanes-ethyl acetate) to afford the title compound as a white solid (0.41 g, 50% yield).
Reaction SMILES: [OH:1][C@@H:2]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:3]([N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:4].O.C(O)(=O)C>C(O)C.[Rh]>[CH:12]1([CH2:11][C@H:2]([OH:1])[C:3]([N:5]2[CH2:6][CH2:7][O:8][CH2:9][CH2:10]2)=[O:4])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: O=C([C@@H](O)Cc1ccccc1)N1CCOCC1
Agent: [Rh]
Solvent: O
Solvent: CC(=O)O
Solvent: CCO
Product: O=C([C@@H](O)CC1CCCCC1)N1CCOCC1
Temperature: 50 °C
Reaction time: 8 h
Yield: 88.5 %

Procedure:
A solution of 2 (20.5 g, 87.1 mmol) in a mixture of ethanol (80 mL), water (10 mL) and acetic acid (10 mL) is charged to a Parr bomb and treated with 2 g of 10% Rh/C. The bomb is sealed, evacuated and pressurized to 1000 psi with hydrogen. The reaction is then heated to 50° C. with stirring overnight. After cooling to room temperature and relieving the pressure, the bomb is evacuated and back filled with nitrogen twice. The reaction mixture is filtered through a pad of celite and the solvent is removed to afford 18.6 g (88.5%) of (S)-3-cyclohexyl-2-hydroxy-1-morpholin-4-yl-propan-1-one (3) as an oil; HPLC-MS calculated for C13H23NO3 (M+H+) 242.2, found 242.4.
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[O:14][CH:15]=[C:16]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[N:17]=2)=[CH:9][CH:8]=1>C(Cl)Cl>[Cl:3][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[O:14][CH:15]=[C:16]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[N:17]=2)=[CH:9][CH:8]=1
Reactant: CCOC(=O)c1coc(-c2ccc(CO)cc2)n1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: CCOC(=O)c1coc(-c2ccc(CCl)cc2)n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 96 %

Procedure:
To a solution of methylene chloride at −10° C. and excess thionyl chloride was added portionwise ethyl 2-[4-(hydroxymethyl)phenyl]-1,3-oxazole-4-carboxylate (1 eq) and the resulting mixture was stirred at room temperature for 3 h. The solvent was removed and the residue was azeotroped with toluene, dissolved in methylene chloride, washed with aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and evaporated to give a yield of 96% of the product as white crystals; m.p. 115-117° C. 1H NMR (300 MHz, CDCl3, δ): 8.28 (s, 1H), 8.12 (d, 2H, J=8.5 Hz), 7.50 (d, 2H, J=8.5 Hz), 4.62 (s, 2H), 4.43 (m, 2H, J=7.4 Hz), 1.41 (t, 3H, J=7.4 Hz).
Reaction SMILES: [CH3:1][C:2](=[CH:4][CH3:5])[CH3:3].[OH:6][C:7]1[CH:20]=[C:19]([OH:21])[CH:18]=[CH:17][C:8]=1[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:10].CS(O)(=O)=O.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[OH:6][C:7]1[CH:20]=[C:19]([OH:21])[C:18]([C:2]([CH3:3])([CH3:1])[CH2:4][CH3:5])=[CH:17][C:8]=1[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:10]
Reactant: CC=C(C)C
Reactant: O=C(c1ccccc1)c1ccc(O)cc1O
Agent: CS(=O)(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCC(C)(C)c1cc(C(=O)c2ccccc2)c(O)cc1O
Reaction time: 6 h
Yield: 89.8 %

Procedure:
42 g (0.6.mol) of 2-methyl-2-butene are added dropwise to a solution of 45 g (0.21 mol) of 2,4-dihydroxybenzophenone and 6.1 g (63 mmol) of methanesulfonic acid in 90 ml of toluene and the mixture is held at 75° C. with stirring for 6 h. The reaction mixture is cooled, then treated with 100 ml of NaHCO3 and extracted with ethyl acetate. The resulting solution is washed with water and then with saturated sodium chloride solution. The residue which remains after drying over MgSO4, filtering and concentrating by evaporation is recrystallized from CH2Cl2 /hexane. 53.6 g (89.9%) of 2,4-dihydroxy-5-(1,1-dimethylpropyl)benzophenone are obtained as beige crystals having a melting point of 100°-104° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[O:19][CH3:20])=[O:11].Cl.O.N([O-])=O.[Na+].[N-:27]=[N+:28]=[N-].[Na+]>>[OH:1][C:2]1[CH:7]=[C:6]([N:8]=[N+:27]=[N-:28])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[O:19][CH3:20])=[O:11]
Reactant: COc1ccccc1NC(=O)Nc1ccc(N)cc1O
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: COc1ccccc1NC(=O)Nc1ccc(N=[N+]=[N-])cc1O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 35.7 %

Procedure:
The N-(2-hydroxy-4-aminophenyl)-N′-(2-methoxyphenyl)urea (300 mg, 1.17 mmol) was added to HCl/H2O (1.17 mL/2.34 mL), cooled to 0° C. Sodium nitrite (80.7 mg, 1.17 mmol) was added to the reaction mixture. The reaction mixture was stirred at 0° C. for 30 minutes. The sodium azide (76 mg, 1.17 mmol) was added to reaction mixture and it was warmed to room temperature. The reaction mixture was stirred at room temperature for 18 hours. Then it was extracted with three times by ethyl acetate. The organic extracts were combined, dried over MgSO4, filtered and concentrated under reduced pressure and chromatography of the resulting solid on silica gel (hexane:ethyl acetate; 5:1) gave product (125 mg, 38%). EI-MS m/z 300 (M+H)+.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]([N:18]([CH2:26][CH3:27])[CH2:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N:8][C:9]2[C:14]([CH:15]=1)=[CH:13][C:12]([F:16])=[C:11]([F:17])[CH:10]=2)=O)C.CC[O-].[Na+].C(O)(=O)C.O>C(O)C>[CH2:24]([O:23][C:21]([CH:20]1[CH2:19][N:18]([CH2:26][CH3:27])[C:7]2[N:8]=[C:9]3[CH:10]=[C:11]([F:17])[C:12]([F:16])=[CH:13][C:14]3=[CH:15][C:6]=2[C:4]1=[O:3])=[O:22])[CH3:25]
Reactant: CCOC(=O)CCN(CC)c1nc2cc(F)c(F)cc2cc1C(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: CC(=O)O
Product: CCOC(=O)C1CN(CC)c2nc3cc(F)c(F)cc3cc2C1=O
Temperature: 20 °C
Reaction time: 1 h
Yield: 87.7 %

Procedure:
A solution of 68 g of 3-ethoxycarbonyl-6,7-difluoro-2-[N-ethyl N-(b-ethoxycarbonylethyl)amino]quinoline in 200 cm3 of absolute ethanol is introduced in the course of 60 minutes into a solution of 16.1 g of sodium ethylate brought to reflux in 600 cm3 of absolute ethanol. The suspension obtained, still refluxing, is stirred for a further 60 minutes. 20 cm3 of glacial acetic acid are then introduced in the course of 30 minutes. The reaction mixture is stirred for a further 15 minutes and, with the mixture still refluxing, 400 cm3 of water are then introduced in the course of 45 minutes. The suspension obtained is cooled to approximately 20° C. The precipitate obtained is drained at approximately 20° C. and washed with twice 200 cm3 of water. The wet product is dried under reduced pressure (20 kPa) at approximately 50° C. 52.4 g of 3-ethoxycarbonyl -7,8-difluoro-1-ethyl-4-oxo-1,2,3,4-tetrahydro-benzo[b][1,8]naphthyridine are isolated in the form of a golden-yellow solid, melting point 152° C.
Reaction SMILES: [BH4-].[Na+].[CH3:3][C:4]([CH3:29])([CH3:28])[C:5](=[O:27])[CH2:6][NH:7][C:8]([C:10]1[C:11]([S:16][CH2:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)=[N:12][CH:13]=[CH:14][CH:15]=1)=[O:9].CCCCCC.CC(=O)OCC>CCO>[F:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][CH2:18][CH2:17][S:16][C:11]2[C:10]([C:8]([NH:7][CH2:6][CH:5]([OH:27])[C:4]([CH3:28])([CH3:3])[CH3:29])=[O:9])=[CH:15][CH:14]=[CH:13][N:12]=2)=[CH:21][CH:22]=1
Reactant: CC(C)(C)C(=O)CNC(=O)c1cccnc1SCCCc1ccc(F)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CC(C)(C)C(O)CNC(=O)c1cccnc1SCCCc1ccc(F)cc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 91.1 %

Procedure:
70 mg (1.8 mmol) of NaBH4 were added in portions at 0° C. to a solution of 350 mg (0.9 mmol) of N-(3,3-dimethyl-2-oxo-butyl)-2-[3-(4-fluoro-phenyl)-propylsulfanyl]-pyridine-3-carboxylic acid amide (exemplary compound 125) in EtOH (7 ml). Stirring was then carried out for 2 h at RT. The mixture was then cooled to 0° C., quenched with a sat. aq. NH4Cl sol. (20 ml) and concentrated in vacuo. The residue was taken up in EA and the solution was washed with a 1M aq. NaHCO3 sol., water and brine, dried over Na2SO4, filtered and concentrated in vacuo. CC (hexane/EA 3:2) of the residue yielded 320 mg (0.82 mmol, 91%) of 2-[3-(4-fluorophenyl)-propylsulfanyl]-N-(2-hydroxy-3,3-dimethyl-butyl)-pyridine-3-carboxylic acid amide. MS: m/z 391.2 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:24]2[O:23][C:10]3[C:11](=[O:22])[N:12]([C@@H:14]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:15]([OH:17])=O)[CH2:13][C:9]=3[CH2:8][C:7]=2[C:6]([O:25][CH3:26])=[CH:5][CH:4]=1.CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:45]2N=CC=[CH:49][C:44]=2N=N1.[NH2:58][C:59]1[CH:64]=[CH:63][C:62]([Cl:65])=[CH:61][N:60]=1>O1CCCC1.O>[Cl:65][C:62]1[CH:63]=[CH:64][C:59]([NH:58][C:15](=[O:17])[C@@H:14]([N:12]2[CH2:13][C:9]3[CH2:8][C:7]4[C:6]([O:25][CH3:26])=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:24]=4[O:23][C:10]=3[C:11]2=[O:22])[CH2:18][CH:19]2[CH2:21][CH2:49][CH2:44][CH2:45][CH2:20]2)=[N:60][CH:61]=1
Reactant: Nc1ccc(Cl)cn1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: COc1ccc(OC)c2c1CC1=C(O2)C(=O)N([C@@H](CC(C)C)C(=O)O)C1
Agent: F[P-](F)(F)(F)(F)F
Solvent: O
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Product: COc1ccc(OC)c2c1CC1=C(O2)C(=O)N([C@@H](CC2CCCCC2)C(=O)Nc2ccc(Cl)cn2)C1
Temperature: 90 °C
Yield: 25.2 %

Procedure:
A solution of (S)-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (Example 13, step 2c) (100 mg, 0.24 mmol), in tetrahydrofuran (10 mL) was treated with N-methylmorpholine (100 mg, 0.74 mmol), 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HATU) (284 mg, 0.74 mmol) and commercially available 2-amino-5-chloropyridine (38 mg, 0.29 mmol). The mixture was heated in a sealed tube was heated for 16 hours at 90° C. The reaction mixture was diluted with water and extracted with ethyl acetate (3×). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue, upon silica gel flash chromatography using hexane-ethyl acetate gradient elution, afforded ((S)—N-(5-chloro-pyridin-2-yl)-3-cyclohexyl-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide (31 mg, 24.4%), as a white solid. 1H NMR (DMSO-d6) δ: 11.05 (br. s., 1H), 8.39 (br. s., 1H), 8.04 (d, J=8.3 Hz, 1H), 7.89 (d, J=8.8 Hz, 1H), 6.91 (d, J=8.8 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 5.08 (d, J=5.9 Hz, 1H), 4.37 (d, J=19.1 Hz, 1H), 4.02 (d, J=18.6 Hz, 1H), 3.76 (s, 6H), 3.55 (br. s., 2H), 1.53-1.85 (m, 7H), 0.75-1.29 (m, 6H).
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([CH2:14][O:15]C(Cl)=O)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH2:19][C@H:20]1[CH2:43][CH2:42][C@@:41]2([CH3:44])[C@H:22]([CH2:23][CH2:24][C@@H:25]3[C@@H:40]2[CH2:39][CH2:38][C@@:37]2([CH3:45])[C@H:26]3[CH2:27][CH2:28][C@@H:29]2[C@H:30]([CH3:36])[CH2:31][CH2:32][C:33]([OH:35])=[O:34])[CH2:21]1.O>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][NH:19][C@H:20]3[CH2:43][CH2:42][C@@:41]4([CH3:44])[C@H:22]([CH2:23][CH2:24][C@@H:25]5[C@@H:40]4[CH2:39][CH2:38][C@@:37]4([CH3:45])[C@H:26]5[CH2:27][CH2:28][C@@H:29]4[C@H:30]([CH3:36])[CH2:31][CH2:32][C:33]([OH:35])=[O:34])[CH2:21]3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(Cl)OCC1c2ccccc2-c2ccccc21
Reactant: C[C@H](CCC(=O)O)[C@H]1CC[C@H]2[C@@H]3CC[C@@H]4C[C@@H](N)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: C[C@H](CCC(=O)O)[C@H]1CC[C@H]2[C@@H]3CC[C@@H]4C[C@@H](NOCC5c6ccccc6-c6ccccc65)CC[C@]4(C)[C@H]3CC[C@]12C
Yield: 69 %

Procedure:
A solution of 9-fluorenylmethoxycarbonyl chloride (0.76 g; 2.93 mmol) in 1,4-dioxane (9 mL) was added dropwise to a suspension of (3β,5β)-3-aminocholan-24-oic acid B (1.0 g; 2.66 mmol) in 10% aq. Na2CO3 (16 mL) and 1,4-dioxane (9 mL) stirred at 0° C. After 6 h stirring at room temperature H2O (90 mL) was added, the aqueous phase washed with Et2O (2×90 mL) and then 2 M HCl (15 mL) was added (final pH: 1.5). The aqueous phase was extracted with EtOAc (2×100 mL), the organic phase dried over Na2SO4 and evaporated. The crude was purified by flash chromatography to give C as a white solid (1.2 g; 2.0 mmol). Yield 69%.