Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.Cl[CH2:3][C:4]1[C:5]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2[O:14][CH3:15].CN(C=O)C.[N-:28]=[N+:29]=[N-:30].[Na+]>>[N:28]([CH2:3][C:4]1[C:5]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2[O:14][CH3:15])=[N+:29]=[N-:30]
Reactant: [N-]=[N+]=[N-]
Reactant: COc1cccc2cc(CCl)c(-c3cccc(F)c3)nc12
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cccc2cc(CN=[N+]=[N-])c(-c3cccc(F)c3)nc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirring solution of 3-(chloromethyl)-2-(3-fluorophenyl)-8-methoxyquinoline hydrochloride (0.9601 g, 2.839 mmol) in DMF (14.19 mL, 2.839 mmol) was added sodium azide (0.3691 g, 5.678 mmol) at room temperature and the mixture was stirred at room temperature After 1 h, the mixture was partitioned between EtOAc (100 mL) and H2O (100 mL). The organic layer was washed with brine (100 mL×1), dried over Na2SO4, filtered, and concentrated under reduced pressure to give 3-(azidomethyl)-2-(3-fluorophenyl)-8-methoxyquinoline as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.48 (1 H, s), 7.54-7.62 (3 H, m), 7.43-7.49 (2 H, m), 7.32-7.39 (1 H, m), 7.21-7.28 (1 H, m), 4.68 (2 H, s), 3.97 (3 H, s); LC-MS (ESI) m/z 309.1 [M+H]+. The yellow solid was carried on crude without purification for the next step.
Reaction SMILES: Cl.[CH2:2]([O:6][C:7](=[O:24])[CH2:8][C:9]1[C:10]([N:21]([CH3:23])[CH3:22])=[N:11][NH:12][C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[CH2:3]CC.Cl>C(O)C>[ClH:20].[CH2:2]([O:6][C:7](=[O:24])[CH2:8][C:9]1[C:10]([N:21]([CH3:22])[CH3:23])=[N:11][NH:12][C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[CH3:3]
Reactant: CCCCOC(=O)Cc1c(N(C)C)n[nH]c1-c1ccc(Cl)cc1
Agent: Cl
Solvent: CCO
Product: CCOC(=O)Cc1c(N(C)C)n[nH]c1-c1ccc(Cl)cc1
Yield: 120.1 %

Procedure:
A solution of 5.6 g (0.015 mole) of 5-(4-chlorophenyl)-3-dimethylamino-1H-pyrazole-4-acetic acid butyl ester monohydrochloride in 150 ml of 200 ethanol was treated with 1 ml of concentrated hydrochloric acid and heated at reflux for 24 hours. The reaction mixture was concentrated in vacuo to a solid residue, 5.5 g. Recrystallization from 2-propanol yielded 3.1 g (60%) of white crystalline product, mp 211°-215° C. with degassing.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[CH:12]=[CH:11][CH:10]=[C:9]3[N:5]2[C:6]=1[C:7](=[O:27])[N:8]3[CH2:13][CH2:14][CH2:15][N:16]1C(=O)C2=CC=CC=C2C1=O.O.NN>C(O)C>[NH2:16][CH2:15][CH2:14][CH2:13][N:8]1[C:9]2[N:5]3[C:4](=[N:3][C:2]([CH3:1])=[C:6]3[C:7]1=[O:27])[CH:12]=[CH:11][CH:10]=2
Reactant: Cc1nc2cccc3n(CCCN4C(=O)c5ccccc5C4=O)c(=O)c1n23
Agent: NN
Solvent: CCO
Solvent: O
Product: Cc1nc2cccc3n(CCCN)c(=O)c1n23
Yield: 75.8 %

Procedure:
To a suspension of 3.47 g (9.63 mmol) of 1,2-dihydro-3-methyl-1-[3-(phthalimido)propan-1-yl]-1,4,7b-triazacyclopent[cd]inden-2-one in 70 ml of ethanol was added 1.45 g (29.0 mmol) of hydrazine monohydrate. The mixture was heated for 2 hours under reflux. After cooling, and the resulting precipitates were filtered off. The filtrate was concentrated to give the residue, water was added, extracted with chloroform (three times). The extract was dried over anhydrous magnesium sulfate, then the solvent was distilled off to give 1.68 g of the desired compound (75.8%, pale yellow solid substance).
Reaction SMILES: Cl[C:2]([C:4]1[S:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[C:5]=1[S:13]([Cl:16])(=[O:15])=[O:14])=[O:3].[CH3:17][OH:18]>C(Cl)(Cl)Cl>[CH3:17][O:18][C:2]([C:4]1[S:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[C:5]=1[S:13]([Cl:16])(=[O:14])=[O:15])=[O:3]
Reactant: CO
Reactant: O=C(Cl)c1sc2ccccc2c1S(=O)(=O)Cl
Solvent: ClC(Cl)Cl
Product: COC(=O)c1sc2ccccc2c1S(=O)(=O)Cl
Yield: 53.5 %

Procedure:
168.0 gm (0.569 mol) of 2-chlorocarbonyl-benzo[b]thiophene-3-sulfonic acid chloride were dissolved in 1 liter of anhydrous chloroform, and the solution was admixed with 27.5 gm (0.858 mol) of dry methanol and refluxed for 3 hours. The reaction mixture was evaporated in vacuo, and the residue was recrystallized twice from a little methanol, yielding 88.5 gm (53.5% of theory) of colorless 2-methoxycarbonyl-benzo[b]-thiophene-3-sulfonic acid chloride. M.p.: 100°-101° C.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.CCN(CC)CC.[C:20]1(=O)[O:25][C:23](=[O:24])[C:22]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:21]12>C1(C)C=CC=CC=1>[O:24]=[C:23]1[C:22]2[C:21](=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:20](=[O:25])[N:1]1[CH:2]1[CH2:3][CH2:4][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:7]1
Reactant: O=C1OC(=O)c2ccccc21
Reactant: CCOC(=O)C1CCC(N)CC1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CCOC(=O)C1CCC(N2C(=O)c3ccccc3C2=O)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 34.1 %

Procedure:
A solution of ethyl 4-aminocyclohexanecarboxylate (0.50 g, 2.92 mmol) in toluene (10 mL) was added Et3N (1.02 mL, 7.30 mmol) and phthalic anhydride (0.56 g, 3.80 mmol) and the mixture refluxed for 6-8 h using dean-stark apparatus to remove water. After completion of the reaction (by TLC), the solvent was evaporated under reduced pressure, water (50 mL) added and stirred for 30 min at rt. The solid material thus obtained was collected by filtration under vacuum and dried to obtain the desired product as off-white solid (0.30 g, 34%). 1H NMR (DMSO-d6): δ 7.84 (s, 4H), 4.19 (q, J=7.20 Hz, 2H), 3.71 (m, 1H), 2.71 (m, 1H), 2.06 (m, 2H), 1.90 (m, 2H), 1.69 (m, 2H), 1.60 (m, 2H), and 1.23 (t, J=7.20 Hz, 3H).
Reaction SMILES: [ClH:1].Cl.[C:3]([C:6]1[CH:28]=[CH:27][CH:26]=[CH:25][C:7]=1[NH:8][C:9](=[O:24])[CH2:10][N:11]1[CH2:16][CH2:15][N:14](CC2C=CC=CC=2)[CH2:13][CH2:12]1)(=[O:5])[NH2:4].O>[C].[Pd].CO>[ClH:1].[ClH:1].[C:3]([C:6]1[CH:28]=[CH:27][CH:26]=[CH:25][C:7]=1[NH:8][C:9](=[O:24])[CH2:10][N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)(=[O:5])[NH2:4]
Reactant: NC(=O)c1ccccc1NC(=O)CN1CCN(Cc2ccccc2)CC1
Agent: [Pd]
Agent: Cl
Solvent: O
Solvent: CO
Product: NC(=O)c1ccccc1NC(=O)CN1CCNCC1

Procedure:
50 Grams of o-carbamoyl-α-(4-benzyl-1-piperazinyl)acetanilide dihydrochloride, 4 g of 10%-palladium carbon, 70 ml of water and 300 ml of methanol were mixed together and the mixture was subjected to catalytic reduction at a room temperature. Then the catalyst was removed from the mother liquor, and the mother liquor was concentrated to dryness. The residue obtained was crystallized by adding acetone, and recrystallized from water-acetone to obtain 35.2 g of o-carbamoyl-α-(1-piperazinyl)acetanilide dihydrochloride. Colorless cotton fiber-like crystals. Melting point: 239.5°-242° C. (decomposed).
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([C:18]3[CH:23]4[CH2:24][CH:20]([CH2:21][CH2:22]4)[C:19]=3[CH2:25][C:26]3[CH:27]=[C:28]([CH:33]=[CH:34][CH:35]=3)[C:29]([O:31]C)=[O:30])[O:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>CO.C1COCC1>[C:1]1([C:7]2[N:8]=[C:9]([C:18]3[CH:23]4[CH2:24][CH:20]([CH2:21][CH2:22]4)[C:19]=3[CH2:25][C:26]3[CH:27]=[C:28]([CH:33]=[CH:34][CH:35]=3)[C:29]([OH:31])=[O:30])[O:10][C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)c1cccc(CC2=C(c3nc(-c4ccccc4)c(-c4ccccc4)o3)C3CCC2C3)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1cccc(CC2=C(c3nc(-c4ccccc4)c(-c4ccccc4)o3)C3CCC2C3)c1
Reaction time: 0.08 h
Yield: 103.1 %

Procedure:
To a solution of methyl 3-{[3-(4,5-diphenyloxazol-2-yl)bicyclo[2.2.1]hept-2-en-2-yl]methyl}benzoate (1.0 g) in a mixture of methanol (10 ml) and THF (10 ml) was added 1N-NaOH solution (11 ml). After being stirred for 5 minutes, the solvent was removed in vacuo. The residue was dissolved in a mixture of ethyl acetate and 1N-HCl solution. The organic layer was washed with brine and dried over MgSO4. The solution was evaporated in vacuo to give 3-{[3-(4,5-diphenyloxazol-2-yl)bicyclo[2.2.1]hept-2-en-2-yl]methyl}-benzoic acid (1.0 g).
Reaction SMILES: [Br:1][CH2:2][C:3](Br)=[O:4].[NH2:6][C:7]1[C:8]([C:13]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[O:14])=[N:9][O:10][C:11]=1[CH3:12].C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>ClCCl.O>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]([C:8]2[C:7]([NH:6][C:3](=[O:4])[CH2:2][Br:1])=[C:11]([CH3:12])[O:10][N:9]=2)=[O:14])=[CH:16][CH:17]=1
Reactant: Cc1onc(C(=O)c2ccc(Cl)cc2)c1N
Reactant: O=C(Br)CBr
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: Cc1onc(C(=O)c2ccc(Cl)cc2)c1NC(=O)CBr
Reaction time: 1 h

Procedure:
Bromoacetyl bromide (39 g, 194 mmoles) was added slowly to a mixture of (4-amino-5-methylisoxazol-3-yl)-4-chlorophenylmethanone of Example Vb (22.9 g, 97 mmoles) in dichloromethane (200 ml) with 2N sodium carbonate (200 ml) and saturated sodium bicarbonate (300 ml) at 5° C. After stirring for 1 hour, the mixture was diluted with dichloromethane (400 ml) and water (400 ml). The organics were washed with water, saturated sodium chloride, dried (sodium sulfate) and evaporated to give 34 g of a solid. The residue (3.0 g) was flash chromatographed (25% ethyl acetate:hexane) to yield 2.4 g (80%) of a solid, melting point 107°-110° C.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]([O:10][C:11]1[CH:12]=[C:13]([C@@H:24]([OH:27])[CH2:25][OH:26])[C:14]2[S:18][C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[N:16][C:15]=2[CH:23]=1)([CH3:9])([CH3:8])[CH3:7]>N1C=CC=CC=1>[C:6]([O:10][C:11]1[CH:12]=[C:13]([C@@H:24]([OH:27])[CH2:25][O:26][S:2]([CH3:1])(=[O:4])=[O:3])[C:14]2[S:18][C:17]([O:19][CH:20]([CH3:21])[CH3:22])=[N:16][C:15]=2[CH:23]=1)([CH3:7])([CH3:8])[CH3:9]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)Oc1nc2cc(OC(C)(C)C)cc([C@@H](O)CO)c2s1
Solvent: c1ccncc1
Product: CC(C)Oc1nc2cc(OC(C)(C)C)cc([C@@H](O)COS(C)(=O)=O)c2s1
Temperature: 0 °C
Reaction time: 3.5 h

Procedure:
Methane sulfonylchloride (35 mg) is added to a solution of (R)-1-(5-tert-Butoxy-2-isopropoxy-benzothiazol-7-yl)-ethane-1,2-diol (100 mg) in pyridine (2 ml) at 0° C. The reaction mixture is then stirred at 0° C. for 3.5 hours. The solvent is removed in vacuo, The resulting residue is partitioned between HCl(aq) (2M) and ether. The organics is washed with water (1×), brine (1×), dried over MgSO4, filtered and the solvent removed in vacuo to give the title compound. 1H nmr (CDCl3, 400 MHz); 7.20 (d, 1H), 6.80 (d, 1H), 5.30 (sept, 1H), 5.10 (t, 1H), 4.30 (d, 2H), 3.00 (s, 3H), 1.40 (d, 6H), 1.30 (s, 9H).
Reaction SMILES: [CH3:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[C:9]([CH2:14][CH:15]=[CH2:16])[CH:8]=2)=[CH:4][CH:3]=1>C(OCC)(=O)C.[Pd]>[CH2:14]([C:9]1[CH:8]=[C:7]([O:6][C:5]2[CH:17]=[CH:18][C:2]([CH3:1])=[CH:3][CH:4]=2)[CH:12]=[CH:11][C:10]=1[OH:13])[CH2:15][CH3:16]
Reactant: C=CCc1cc(Oc2ccc(C)cc2)ccc1O
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCCc1cc(Oc2ccc(C)cc2)ccc1O

Procedure:
A solution of 4-(4′-methylphenoxy)-2-allylphenol (2.30 g, 9.42 mmol) and 5% Pd/C (0.90 g) in ethyl acetate (30 mL) was stirred under H2 atmosphere for 3 h at room temperature. The reaction mixture was filtered through a short pad of silica gel and concentrated in vacuo to afford the title compound which was used as is. 1H NMR (400 MHz, CDCl3): δ 7.19 (d, 2H), 6.86 (d, 1H), 6.83 (dd, 2H), 6.72 (d, 2H), 4.61 (s, 1H), 2.53 (t, 2H), 2.30 (s, 3H), 1.61 (hex, 2H), 0.96 (t, 3H).
Reaction SMILES: C[O:2]C(=O)COC1C=C(OC)C(S)=CC=1C.Cl[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][N:26]=2)=[CH:21][CH:20]=1>>[F:32][C:31]([F:34])([F:33])[C:28]1[CH:29]=[CH:30][C:25]([C:22]2[CH:23]=[CH:24][C:19]([CH2:18][OH:2])=[CH:20][CH:21]=2)=[N:26][CH:27]=1
Reactant: COC(=O)COc1cc(OC)c(S)cc1C
Reactant: FC(F)(F)c1ccc(-c2ccc(CCl)cc2)nc1
Product: OCc1ccc(-c2ccc(C(F)(F)F)cn2)cc1

Procedure:
The title compound was prepared in the manner analogous to Example 1F using 1D and 18B. MS m/z 478 (M+1).
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:5]([F:32])=[C:6]([CH:30]=[O:31])[C:7]([C:10]2[C:11]([CH:28]=[O:29])=[C:12]([F:27])[C:13]([O:16][CH2:17][CH:18]3[CH2:23][CH2:22][CH:21]([CH2:24][CH2:25][CH3:26])[CH2:20][CH2:19]3)=[CH:14][CH:15]=2)=[CH:8][CH:9]=1)[CH3:2]>[Zn].[Cl-].[Zn+2].[Cl-].CN(C=O)C>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]2[C:10]3[C:11](=[C:12]([F:27])[C:13]([O:16][CH2:17][CH:18]4[CH2:19][CH2:20][CH:21]([CH2:24][CH2:25][CH3:26])[CH2:22][CH2:23]4)=[CH:14][CH:15]=3)[CH:28]([OH:29])[CH:30]([OH:31])[C:6]=2[C:5]=1[F:32])[CH3:2]
Reactant: CCCC1CCC(COc2ccc(-c3ccc(OCC)c(F)c3C=O)c(C=O)c2F)CC1
Agent: [Cl-]
Agent: [Zn+2]
Agent: [Zn]
Solvent: CN(C)C=O
Product: CCCC1CCC(COc2ccc3c(c2F)C(O)C(O)c2c-3ccc(OCC)c2F)CC1
Yield: 85.3 %

Procedure:
Under a nitrogen atmosphere, zinc powder (1.85 g, 28.30 mmol) and zinc chloride (0.64 g, 4.696 mmol) were added to a DMF (50 mL) solution of compound (63) (4.20 g, 9.449 mmol), and the resultant mixture was agitated at 80° C. for 8 hours. The reaction mixture was quenched with 100 mL of 1N hydrochloric acid aqueous solution, and extracted with 50 mL of toluene three times. Combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine, and then dried over magnesium sulfate, and a solvent was distilled off by an evaporator. The residue was purified by silica gel column chromatography, and thus 2-ethoxy-1,8-difluoro-7-((4-propylcyclohexyl)methoxy)-9,10-dihydrophenanthrene-9,10-diol (64) (3.6 g, yield 85.4%) was obtained.
Reaction SMILES: [Na].[C:2]1([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]=1.[CH2:15]([O:17][C:18](=[O:30])[CH:19](Br)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH3:16]>C(O)C>[CH2:15]([O:17][C:18](=[O:30])[CH:19]([O:14][C:11]1[CH:10]=[CH:9][C:8]([C:2]2[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]=2)=[CH:13][CH:12]=1)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH3:16]
Reactant: Oc1ccc(C2=CCCCC2)cc1
Reactant: CCCCCCCCCC(Br)C(=O)OCC
Agent: [Na]
Solvent: CCO
Product: CCCCCCCCCC(Oc1ccc(C2=CCCCC2)cc1)C(=O)OCC

Procedure:
To a solution of 1.6 g of sodium in 100 ml of absolute ethanol, 10 g of p-(1-cyclohexenyl)-phenol in a small amount of absolute ethanol are added at room temperature under anhydrous conditions and with stirring. 25.2 Grams of α-bromo-undecanoic acid ethyl ester are then added dropwise. and the reaction mixture is stirred for 24 hours at 50° C. The ethanol is subsequently stripped off in vacuo and the residue is partitioned between water and ice-cold N solution hydroxide solution. The organic phase is washed until neutral, dried over sodium sulphate and concentrated in vacuo. The residue yields the crude α-[p-(1-cyclohexenyl)-phenoxy]-undecanoic acid ethyl ester of the formula ##STR19## in the form of an oil.
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[CH:7]=[C:8]([C:25]1[S:26][C:27]2[CH:33]=[CH:32][CH:31]=[CH:30][C:28]=2[N:29]=1)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[CH2:21][CH2:20][CH2:19][NH:18][C:17]=2[N:16]=1)([CH3:4])([CH3:3])[CH3:2].[H][H]>[Pd].CO.C(O)C>[C:1]([O:5][C:6](=[O:34])[CH2:7][CH:8]([C:25]1[S:26][C:27]2[CH:33]=[CH:32][CH:31]=[CH:30][C:28]=2[N:29]=1)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[CH2:21][CH2:20][CH2:19][NH:18][C:17]=2[N:16]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)C=C(CCCCCCc1ccc2c(n1)NCCC2)c1nc2ccccc2s1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Solvent: CCO
Product: CC(C)(C)OC(=O)CC(CCCCCCc1ccc2c(n1)NCCC2)c1nc2ccccc2s1

Procedure:
To a stirred suspension of 10% palladium on carbon (50 mg) in methanol (5 mL) was added a solution of 3-(benzothiazol-2-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-non-2-enoic acidtert-butyl ester 29-7c (190 mg) in ethanol (5 mL) and the mixture was subjected to an atmosphere of hydrogen for 48 hours. The reaction mixture was filtered through Celite and concentrated at reduced pressure. The resulting oil was purified by flash column chromatography over silica gel with 4:1 hexanes/acetone to give 29-8c as a colorless oil.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:56][CH2:55][C@@:54]2([CH3:57])[C@H:4]([CH2:5][C@@H:6]([OH:60])[C@@H:7]3[C@@H:53]2[CH2:52][C@H:51]([OH:58])[C@@:50]2([CH3:59])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:49])[CH2:13][CH2:14][C:15]([O:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]3[C:30]([Cl:31])=[CH:29][C:28]([NH:32][C:33](=[O:44])[C:34]([O:36]CC4C=CC=CC=4)=[O:35])=[CH:27][C:26]=3[Cl:45])=[CH:20][C:19]=2[CH:46]([CH3:48])[CH3:47])=[O:16])[CH2:3]1.[H][H]>[Pd].C(O)C>[OH:1][C@@H:2]1[CH2:56][CH2:55][C@@:54]2([CH3:57])[C@H:4]([CH2:5][C@@H:6]([OH:60])[C@@H:7]3[C@@H:53]2[CH2:52][C@H:51]([OH:58])[C@@:50]2([CH3:59])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:49])[CH2:13][CH2:14][C:15]([O:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]3[C:26]([Cl:45])=[CH:27][C:28]([NH:32][C:33](=[O:44])[C:34]([OH:36])=[O:35])=[CH:29][C:30]=3[Cl:31])=[CH:20][C:19]=2[CH:46]([CH3:48])[CH3:47])=[O:16])[CH2:3]1
Reactant: [H][H]
Reactant: CC(C)c1cc(Oc2c(Cl)cc(NC(=O)C(=O)OCc3ccccc3)cc2Cl)ccc1OC(=O)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3C[C@H](O)[C@]12C
Agent: [Pd]
Solvent: CCO
Product: CC(C)c1cc(Oc2c(Cl)cc(NC(=O)C(=O)O)cc2Cl)ccc1OC(=O)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3C[C@H](O)[C@]12C

Procedure:
4-{4-[(2-benzyloxy-1,2-dioxoethyl)amino]-2,6-dichlorophenoxy}-2-isopropylphenyl 3,7,12(3α,5β,7α, 12α)-trihydroxycholan-24-oate (260 rag) and 26 mg of 10% palladium on carbon in 50 ml ethanol are treated with hydrogen on a Parr shaker. Catalyst is removed by filtering through Celite and the filtrate is stripped to give 4-{2,6-dichloro-4-[(2-hydroxy-1,2-dioxoethyl) amino]phenoxy}-2-isopropylphenyl 3,7, 12(3α,5β,7α, 12α)-trihydroxycholan-24-oate, as an amorphane monohydrate, m.p. 180°-92° (dec.).
Reaction SMILES: [N+:1]([C:4]1[CH:25]=[CH:24][CH:23]=[C:6]2[C:7]([N:9]([C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([OH:22])[CH:20]=4)[CH:15]=[CH:14][CH:13]=3)[C:10](=[O:11])[C:5]=12)=[O:8])([O-])=O.[N-:26]=[N+:27]=[N-].[Na+].O>CS(C)=O>[N:1]([C:4]1[CH:25]=[CH:24][CH:23]=[C:6]2[C:7]([N:9]([C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([OH:22])[CH:20]=4)[CH:15]=[CH:14][CH:13]=3)[C:10](=[O:11])[C:5]=12)=[O:8])=[N+:26]=[N-:27]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C1c2cccc([N+](=O)[O-])c2C(=O)N1c1cccc2ccc(O)cc12
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: [N-]=[N+]=Nc1cccc2c1C(=O)N(c1cccc3ccc(O)cc13)C2=O
Temperature: 80 °C
Reaction time: 24 h
Yield: 73.5 %

Procedure:
A mixture of 2.4 g (0.007 mol) of 1-(3-nitrophthalimidyl)-7-hydroxynaphthalene and 0.52 g (0.008 mol) of sodium azide in 14 ml of dimethylsulphoxide is stirred for 24 hours at 80° C. 100 ml of water are added to the solution. The crystals which have precipitated are filtered off with suction, washed with water and dried at 80° C./100 mm Hg. 1.7 g (73.6% of theory) of 1-(3-azidophthalimidyl)-7-hydroxynaphthalene are obtained; melting point 154° C. (with decomposition). IR spectrum (KBr): 1775 and 1720 cm-1 (CO--N--CO); 2130 cm-1 (N3).
Reaction SMILES: [C:1]1([S:7][C:8]2[C:9]([NH:24][C:25]3[S:29][N:28]=[C:27]([CH:30]4[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]4)[N:26]=3)=[N:10][CH:11]=[C:12]([S:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[CH:22][S:23][C:16]=34)[CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.[ClH:45]>O1CCOCC1>[ClH:45].[ClH:45].[C:1]1([S:7][C:8]2[C:9]([NH:24][C:25]3[S:29][N:28]=[C:27]([CH:30]4[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)[N:26]=3)=[N:10][CH:11]=[C:12]([S:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[CH:22][S:23][C:16]=34)[CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2nsc(Nc3ncc(Sc4ccnc5ccsc45)cc3Sc3ccccc3)n2)CC1
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: c1ccc(Sc2cc(Sc3ccnc4ccsc34)cnc2Nc2nc(C3CCNCC3)ns2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.6 %

Procedure:
Tert-butyl 4-(5-(3-(phenylthio)-5-(thieno[3,2-b]pyridin-7-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidine-1-carboxylate was dissolved in 1:1CH2Cl2:methanol (4 mL) and 4N HCl in dioxane added (2 mL) and stirred at ambient temperature for 1 hour. The solvent was removed and placed on high vacuum to afford the title compound (100 mg, 89.6% yield) as a yellow solid. 1H NMR (d6-DMSO)S 8.70 (m, 2H), 8.20 (m, 3H), 7.95 (m, 1H), 7.40 (m, 5H), 3.80-3.05 (m, 9H). Mass spectrum (apci) m/z=535.2 (M+H-3HCl).
Reaction SMILES: [CH2:1]([O:8][N:9]1[C:18](=[O:19])[C:17]2[CH:20]=[C:21]([Br:26])[C:22]([N+:23]([O-])=O)=[C:15]3[C:16]=2[C:11](=[CH:12][CH:13]=[CH:14]3)[C:10]1=[O:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1[CH2:32][CH2:31][CH2:30][CH2:29]1.C(N(CC)CC)C>CN(C=O)C>[CH2:1]([O:8][N:9]1[C:18](=[O:19])[C:17]2[CH:20]=[C:21]([Br:26])[C:22]([N:23]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[C:15]3[C:16]=2[C:11](=[CH:12][CH:13]=[CH:14]3)[C:10]1=[O:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C1CCNC1
Reactant: O=C1c2cccc3c([N+](=O)[O-])c(Br)cc(c23)C(=O)N1OCc1ccccc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C1c2cccc3c(N4CCCC4)c(Br)cc(c23)C(=O)N1OCc1ccccc1
Yield: 90.1 %

Procedure:
To a solution of 2-benzyloxy-5-bromo-6-nitro-benzo[de]isoquinoline-1,3-dione (0.25 g, 0.59 mmol, from Example S1-A) in DMF (5 mL) was added pyrrolidine (0.05 g, 0.70 mmol) and triethyl amine (0.18 g, 1.8 mmol). The reaction was reacted at 85° C. for 24 hours, cooled, and concentrated under vacuum. The residue was triturated with methanol to give 0.24 g of the title compound.
Reaction SMILES: [C:1]([C:5]1[C:6]([Cl:34])=[C:7]([C:11]2[NH:33][C:14]3[C:15]([O:29][CH2:30][CH2:31][OH:32])=[N:16][C:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[C:25]([F:28])([F:27])[F:26])=[CH:18][C:13]=3[N:12]=2)[N:8]([CH3:10])[N:9]=1)([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[C:1]([C:5]1[C:6]([Cl:34])=[C:7]([C:11]2[NH:33][C:14]3[C:15]([O:29][CH2:30][CH:31]=[O:32])=[N:16][C:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[C:25]([F:28])([F:27])[F:26])=[CH:18][C:13]=3[N:12]=2)[N:8]([CH3:10])[N:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: Cn1nc(C(C)(C)C)c(Cl)c1-c1nc2cc(-c3ccccc3C(F)(F)F)nc(OCCO)c2[nH]1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: Cn1nc(C(C)(C)C)c(Cl)c1-c1nc2cc(-c3ccccc3C(F)(F)F)nc(OCC=O)c2[nH]1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a suspension of 2-[2-(5-tert-butyl-4-chloro-2-methyl-2H-pyrazol-3-yl)-6-(2-trifluoromethyl-phenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy]-ethanol (230 mg, 0.466 mmol, prepared as described in Example 11, STEP F) in DCM (10 mL) at 0° C. was added Dess-Martin periodinane (395 mg, 0.931 mmol). The resulting mixture was warmed to room temperature and stirred for 2 h. The reaction was then quenched by adding aqueous 10% Na2S2O3 solution (20 mL). The resulting mixture was treated with EtOAc (50 mL) and washed with saturated NaHCO3 solution (20 mL), H2O (20 mL) and brine (20 mL). After drying with Na2SO4, the resulting solution was concentrated in vacuo and the residue was purified by flash chromatography on silica gel (20:80-50:50 EtOAc/hexanes) to yield [2-(5-tert-butyl-4-chloro-2-methyl-2H-pyrazol-3-yl)-6-(2-trifluoromethyl-phenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy]-acetaldehyde as a yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 7.67 (dd, J=7.5, 1.9 Hz, 1H), 7.49-7.54 (m, 2H), 7.35-7.44 (m, J=7.3, 7.3, 7.3, 7.3, 1.6 Hz, 2H), 5.07 (t, J=4.9 Hz, 1H), 4.52 (dd, J=4.8, 1.5 Hz, 2H), 4.04 (s, 3H), 1.45 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calculated For C23H21F3N5O2: 492.1 (M+H), Measured: 492.1.