Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Sn]([C:14]1[S:15][CH:16]=[CH:17][CH:18]=1)(CCCC)CCCC)CCC.Cl[C:20]1[CH:25]=[C:24](Cl)[N:23]=[CH:22][N:21]=1>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[S:15]1[CH:16]=[CH:17][CH:18]=[C:14]1[C:20]1[CH:25]=[C:24]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[N:23]=[CH:22][N:21]=1
Reactant: Clc1cc(Cl)ncn1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cccs1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: c1csc(-c2cc(-c3cccs3)ncn2)c1
Yield: 72 %

Procedure:
A mixture of tri-n-butylstannylthiophene (10.52 g, 28.19 mmol), 4,6-dichloropyrimidine (2.00 g, 13.42 mmol), tetrakis(triphenylphosphine)palladium(0) (0.345 g, 0.30 mmol) and few crystals of 2,6-di-tert-butyl-4-methylphenolo in dry toluene (20 mL) was deareated twice with nitrogen. The reaction mixture was refluxed for 6 hours and, after cooling, a white precipitate was formed in the reaction flask. The solid was collected and the organic phase was diluted with ether (100 mL), poured onto a solution of NH4F (3 g, 100 ml) and separated. After drying over MgSO4, the solvent was evaporated affording a solid material. The two solid phase were combined and crystallized from toluene to give the pure product as a white crystals (2.36 g, 9.66 mmol, 72.0% yield). mp 146° C.; 1H NMR (CDCl3) δ 9.07 (1H, d, 2J=1.4), 7.86 (1H, d, 2J=3.7), 7.83 (1H, d), 7.57 (1H, d, 2J=5.1), 7.20 (1H, dd).
Reaction SMILES: Br[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[O:18][CH3:19])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[F:20][C:21]([F:32])([F:31])[C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=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]>[CH3:19][O:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[NH:11][C:9]1[N:10]=[C:3]2[C:2]([C:26]3[CH:25]=[CH:24][CH:23]=[C:22]([C:21]([F:32])([F:31])[F:20])[CH:27]=3)=[CH:7][CH:6]=[CH:5][N:4]2[N:8]=1
Reactant: OB(O)c1cccc(C(F)(F)F)c1
Reactant: COc1ccccc1Nc1nc2c(Br)cccn2n1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Product: COc1ccccc1Nc1nc2c(-c3cccc(C(F)(F)F)c3)cccn2n1

Procedure:
(2-Methoxy-phenyl)-[8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-amine was prepared from (8-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-(2-methoxy-phenyl)-amine (50.0 mg, 0.157 mmol) and (3-trifluoromethylphenyl)boronic acid (33.0 mg, 0.174 mmol) with Pd(dppf)Cl2 (0.012 g) as the catalyst in a manner analogous to Step 2c. The reaction product was isolated as a white solid (0.042 g, 70%). MP=137-141° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.47 (dd, J=6.7, 0.9 Hz, 1H), 8.43 (dd, J=8.0, 1.3 Hz, 1H), 8.34 (s, 1H), 8.25 (d, J=7.4 Hz, 1H), 7.71-7.58 (m, 4H), 7.08-6.98 (m, 4H), 3.93 (s, 3H). MS=385 (MH)+.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N+:10]([O-])=[CH:9][CH:8]=[CH:7]2.[C:13]([O:16]C(=O)C)(=[O:15])[CH3:14]>>[C:13]([O:16][C:9]1[CH:8]=[CH:7][C:6]2[C:11](=[C:2]([OH:1])[CH:3]=[CH:4][CH:5]=2)[N:10]=1)(=[O:15])[CH3:14]
Reactant: [O-][n+]1cccc2cccc(O)c21
Reactant: CC(=O)OC(C)=O
Product: CC(=O)Oc1ccc2cccc(O)c2n1
Temperature: 0 °C
Yield: 84 %

Procedure:
A mixture of 5a (0.81 g, 5 mmol) in acetic anhydride (20 ml) was heated at reflux for 2 h (monitored by TLC). After cooling, it was poured into ice water (100 ml). The resulting solid was collected and crystallized from dichloromethane to give 2-Acetoxy-8-hydroxyquinoline (5b) (0.85 g, 84%) as white crystals. mp: 240°-241° C.; 1H-NMR (DMSO-d6): δ2.55; (s, 3H, CH3), 6.66 (d, 3-H), 7.15-7.23 (m, 3H, Ar--H), 7.78 (d, 4-H), 11.31 (br s, 1H, OH).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:27])[C:5]([N:7]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1)=[O:6])[CH3:2].[C:28](Cl)(=[O:42])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH:36]=[CH:37][CH2:38][CH2:39][CH2:40][CH3:41]>>[O:6]=[C:5]([N:7]([CH2:19][C:20]1[CH:21]=[CH:22][C:23]([NH:26][C:28](=[O:42])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]/[CH:36]=[CH:37]/[CH2:38][CH2:39][CH2:40][CH3:41])=[CH:24][CH:25]=1)[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]([F:16])([F:17])[F:18])=[CH:13][CH:14]=1)[C:4]([O:3][CH2:1][CH3:2])=[O:27]
Reactant: CCCCC=CCCCCCCCC(=O)Cl
Reactant: CCOC(=O)C(=O)N(Cc1ccc(N)cc1)Cc1ccc(C(F)(F)F)cc1
Product: CCCC/C=C/CCCCCCCC(=O)Nc1ccc(CN(Cc2ccc(C(F)(F)F)cc2)C(=O)C(=O)OCC)cc1
Yield: 81 %

Procedure:
The same procedure as employed in the preparation of Example 15, step d using ethyl{(4-aminobenzyl)[4-(trifluoromethyl)benzyl]amino}(oxo)acetate and tetradec-9-enoyl chloride gave the title compound as a colorless oil (81%). M−(LC/MS(ESI)): 588.0. HPLC (Condition A), Rt: 7.3 min (HPLC purity: 96.9%).
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[Cl:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C@@H:14]1[O:18][C:17]([CH3:20])([CH3:19])[O:16][C@H:15]1[C:21](OC)=[O:22]>C1COCC1>[Cl:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C@@H:14]1[O:18][C:17]([CH3:19])([CH3:20])[O:16][C@H:15]1[CH2:21][OH:22]
Reactant: COC(=O)[C@@H]1OC(C)(C)O[C@H]1c1ccccc1Cl
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC1(C)O[C@@H](CO)[C@H](c2ccccc2Cl)O1
Temperature: 25 °C
Yield: 99.9 %

Procedure:
A solution of To a solution LAH(LiAlH4 3.31 g, 87.25 mmol) in THF was added dropwise to a solution of (4R,5S)-methyl 5-(2-chlorophenyl)-2,2-dimethyl-1,3-dioxolane-4-carboxylate (23.6 g, Preparation 26) in THF at 0° C., and the mixture stirred at room temp. The reaction mixture was quenched with H2O at 0° C., cellite filtered with EtOAc, washed with EtOAc, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated. The crude compound was purified by a silica gel column to produce the title compound (21.13 g 70˜95%)
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:13]([O-:15])=[O:14])=[C:6]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[CH:7]=1.CI.[C:18](=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:13]([O-:15])=[O:14])=[C:6]([N:8]([CH3:18])[S:9]([CH3:12])(=[O:10])=[O:11])[CH:7]=1
Reactant: CS(=O)(=O)Nc1cc(F)ccc1[N+](=O)[O-]
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CI
Solvent: O
Product: CN(c1cc(F)ccc1[N+](=O)[O-])S(C)(=O)=O
Reaction time: 24 h

Procedure:
N-(5-fluoro-2-nitrophenyl)methanesulfonamide compound (5 g, 21 mmol), methyl iodide (3 mL) and potassium carbonate (10 g) were stirred together in DMSO (100 mL) at 80° C. overnight. The reaction was not complete and a further 1 mL of methyl iodide was added. After a further 24 hours at 80° C., water (1000 mL) was added. The solution was decanted from a small amount of sticky residue. The product crystallized out from the aqueous solution (48 hours) and was collected by filtration, washed with water and dried. Yield 3.3 g (63%); 1H NMR (400 MHz, CDCl3) δ 3.04 (s, 3H), 3.30 (s, 3H), 7.20 (m, 1H), 7.31 (dd, J=8.54, 2.68 Hz, 1H), 8.0 (dd, J=9.3, 5.6 Hz, 1H); MS (ESI+) for C8H9FN2O4S m/z 248 M+.
Reaction SMILES: [CH2:1]([S:13]([C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22]C)=[O:21])=[CH:18][CH:17]=1)(=[O:15])=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[OH-].[K+].Cl>CO.O>[CH2:1]([S:13]([C:16]1[CH:25]=[CH:24][C:19]([C:20]([OH:22])=[O:21])=[CH:18][CH:17]=1)(=[O:15])=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCS(=O)(=O)c1ccc(C(=O)OC)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCCCCCCCCCCCS(=O)(=O)c1ccc(C(=O)O)cc1
Temperature: 55 °C
Yield: 66.7 %

Procedure:
Methyl 4-dodecylsulfonylbenzoate (5), (approximately 63.43 mMole) was suspended in methanol (100 mL), and 85%-potassium hydroxide (10.5 g, 64.67 mMole) in water (20 mL) added. The mixture was heated to 50-60° C. for 15 minutes during which time the solid went into solution. The solution was then cooled and added to ice cold 2N-HCl (1 L). The white solid was filtered off, washed with water, then methanol and finally air-dried to give 15.0 g of 4-dodecylsulfonylbenzoic acid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:17][C:16](=O)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1.S(Cl)([Cl:21])=O>CN(C)C=O>[Cl:21][C:16]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[N:17]=1
Reactant: O=c1[nH]c(-c2ccc(Cl)cc2)nc2ccccc12
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: Clc1ccc(-c2nc(Cl)c3ccccc3n2)cc1

Procedure:
To a mixture of 15.8 g of 2-(4-chlorophenyl)quinazolin-4(3H)-one and 115 ml of thionyl chloride was added dropwise 4.5 g of dimethylformamide and the mixture was treated as described in Example I to obtain a yellow solid which was recrystallized from cyclohexane to give 13.6 g of light yellow 4-chloro-2-(4-chlorophenyl)quinazoline, m.p. 166°-167°; ir and nmr spectra were consistent with the assigned structure.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[CH2:16][CH2:15][CH2:14][N:13]([S:18]([CH3:21])(=[O:20])=[O:19])[C:12]=3[N:11]=[C:10]([CH:22]([CH3:24])[CH3:23])[C:9]=2[CH:25]=[CH:26][CH:27]2[O:32]C(C)(C)[O:30][CH:29]([CH2:35][C:36]([O-:38])=[O:37])[CH2:28]2)=[CH:4][CH:3]=1.Cl.[OH-].[Na+].O>C1COCC1.CO.CCCCCCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[CH2:16][CH2:15][CH2:14][N:13]([S:18]([CH3:21])(=[O:20])=[O:19])[C:12]=3[N:11]=[C:10]([CH:22]([CH3:23])[CH3:24])[C:9]=2/[CH:25]=[CH:26]/[C@@H:27]([OH:32])[CH2:28][C@@H:29]([OH:30])[CH2:35][C:36]([OH:38])=[O:37])=[CH:4][CH:3]=1
Reactant: CC(C)c1nc2c(c(-c3ccc(F)cc3)c1C=CC1CC(CC(=O)[O-])OC(C)(C)O1)CCCN2S(C)(=O)=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCCCC
Product: CC(C)c1nc2c(c(-c3ccc(F)cc3)c1/C=C/[C@@H](O)C[C@@H](O)CC(=O)O)CCCN2S(C)(=O)=O
Temperature: 15 °C
Reaction time: 2.5 h

Procedure:
A solution of Part G 1,1-dimethylethyl(4R,6S)-(E)-(6-{2-[4-(4-fluorophenyl)-2-isopropyl-8-methanesulfonyl-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl]ethenyl}-2,2-dimethyl-[1,3]dioxan-4-acetate (10.8 g, 0.018 mol) in THF/MeOH (5:2, 140 mL) was cooled to 15° C. An aqueous solution of HCl (6 N, 9.0 mL, 0.054 mol) was added over 15 min. The reaction mixture was stirred at 15° C. for 2.5 h. An aqueous solution of NaOH (2 N, 44.8 mL, 0.090 mol) was added over 15 min at 15° C. The mixture was stirred for an additional 1 h. Water (35 mL) and heptane (100 mL) were added, and the two phases were separated. The aqueous phase was washed with MTBE (30 mL). The aqueous phase was acidified with aqueous HCl (3 N) to pH 2.8, then was extracted with ethyl acetate (2 times, 100 mL and 50 mL). The organic phases were combined and the solvent was removed at 45° C. under reduced pressure until total volume of 100 mL remained. The resulting solution was cooled to 0° C. over 60 min. Seed crystals (30 mg) of Part H compound were added at 0° C. and the resulting slurry was stirred for an additional 30 min. Heptane (80 mL) was added over 30 min, and the slurry was stirred for 1 h at 0° C. The solids were collected by filtration. After drying at 60° C. under vacuum, (E)-(3R,5S)-7-[4-(4-fluorophenyl)-2-isopropyl-8-methanesulfonyl-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl]-3,5-dihydroxyhept-6-enoic acid was obtained as a white solid (8.20 g, 90% yield): mp 184-186° C.; 1H NMR (400 MHz, CDCl3) δ 1.10-1.18 (m, 1H), 1.21 (d, J=5.9 Hz, 6H), 1.35-1.42 (m, 1H), 1.77-1.83 (m, 2H), 2.17 (dd, J=8.1, 8.7 Hz, 1H), 2.23 (dd, J=4.7, 5.4 Hz, 1H), 2.30 (t, J=6.7 Hz, 2H), 3.31 (s, 1H), 3.36-3.41 (m, 1H), 3.58 (s, 3H), 3.71 (s, 1H), 3.77 (t, 2H, J=6.0 Hz), 4.62 (s, 1H), 4.76 (d, J=4.4 Hz, 1H), 5.29 (dd, J=5.7, 5.7 Hz, 1H), 6.18 (d, J=15.2 Hz, 1H), 7.13-7.28 (m, 4H), 12.0 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ172.8, 162.6, 160.2, 159.3, 148.7, 140.5, 134.4, 131.3, 131.1, 125.3, 123.5, 117.3, 115.8, 115.6, 69.3, 65.7, 45.6, 43.9, 43.6, 32.2, 26.3, 23.7, 23.4; HRMS calcd for C25H32FN2O6S (M+1) 507.1965, found 507.1960.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[N:13]([S:14]([C:17]3[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[CH:12]=[CH:11][C:5]2=[N:6][C:7]=1[CH:8]([NH2:10])[CH3:9].Cl[C:25]1[N:30]=[C:29]([NH:31][C:32]2[CH:36]=[C:35]([CH:37]3[CH2:39][CH2:38]3)[NH:34][N:33]=2)[CH:28]=[CH:27][N:26]=1.CCN(C(C)C)C(C)C>CC(C(O)C(C)C)C>[CH:37]1([C:35]2[NH:34][N:33]=[C:32]([NH:31][C:29]3[CH:28]=[CH:27][N:26]=[C:25]([NH:10][CH:8]([C:7]4[N:6]=[C:5]5[CH:11]=[CH:12][N:13]([S:14]([C:17]6[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=6)(=[O:16])=[O:15])[C:4]5=[CH:3][C:2]=4[F:1])[CH3:9])[N:30]=3)[CH:36]=2)[CH2:39][CH2:38]1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3nc(C(C)N)c(F)cc32)cc1
Reactant: Clc1nccc(Nc2cc(C3CC3)[nH]n2)n1
Agent: CC(C)C(O)C(C)C
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(S(=O)(=O)n2ccc3nc(C(C)Nc4nccc(Nc5cc(C6CC6)[nH]n5)n4)c(F)cc32)cc1
Temperature: 135 °C
Yield: 22.5 %

Procedure:
A mixture of 1-(6-fluoro-1-tosyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (500 mg, 1.5 mmol), 2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (353 mg, 1.5 mmol), and DIPEA (581 mg, 4.5 mmol) in 2,4-dimethylpentan-3-ol (2 mL) was heated at 135° C. for 15 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by reverse phase chromatography to afford 180 mg (21%) of N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-(1-(6-fluoro-1-tosyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)pyrimidine-2,4-diamine as a white solid. MS (ESI): m/z=533.3 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][O:13][C@@H:14]2[CH2:19][CH2:18][CH2:17][C@H:16]([O:20][CH2:21][C:22]3[N:23]=[C:24]([C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=4)[O:25][C:26]=3[CH3:27])[CH2:15]2)[C:3]=1[C:4]([O:6]C)=[O:5].[OH-].[K+]>C(O)(C)C.O>[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][O:13][C@@H:14]2[CH2:19][CH2:18][CH2:17][C@H:16]([O:20][CH2:21][C:22]3[N:23]=[C:24]([C:28]4[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=4)[O:25][C:26]=3[CH3:27])[CH2:15]2)[C:3]=1[C:4]([OH:6])=[O:5]
Reactant: COC(=O)c1c(C)cccc1CO[C@@H]1CCC[C@H](OCc2nc(-c3ccc(C)cc3)oc2C)C1
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Product: Cc1ccc(-c2nc(CO[C@H]3CCC[C@@H](OCc4cccc(C)c4C(=O)O)C3)c(C)o2)cc1
Temperature: 95 °C
Reaction time: 24 h
Yield: 57 %

Procedure:
from methyl methyl-6-[(1R,3S)-3-(5-methyl-2-p-tolyloxazol-4-ylmethoxy)-cyclohexyloxymethyl]benzoate: 97.1 g (165 mmol) of methyl methyl-6-[(1R,3S)-3-(5-methyl-2-p-tolyloxazol-4-ylmethoxy)cyclohexyloxymethyl]benzoate are dissolved in a mixture of 640 ml of isopropanol and 80 ml of water. 47.7 g (809 mmol) of potassium hydroxide are added in portions. The reaction is stirred at 95° C. for 24 hours. Subsequently, the solvent is removed fully under reduced pressure and the residue is taken up in 800 ml of tert-butyl methyl ether and 800 ml of water. Addition of hydrochloric acid (2 M) acidifies the mixture. After phase separation, the organic phase is washed four times with 200 ml each time of water. The organic phase is concentrated under reduced pressure and the residue is stirred with a little diisopropyl ether. The solid is filtered and dried under reduced pressure. 2-methyl-6-[(1R,3S)-3-(5-methyl-2-p-tolyloxazol-4-ylmethoxy)-cyclohexyloxymethyl]benzoic acid is obtained in 57% yield as a crystalline solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[NH:10][C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH3:12])=[CH:5][C:4]=1[N+:26]([O-])=O.[BH4-].[Na+]>O.O.O.O.O.O.[Ni](Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)[NH:10][C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH3:12])=[CH:5][C:4]=1[NH2:26]
Reactant: COc1ccc(C(N[C@@H](C)c2ccccc2)c2ccc(F)cc2)cc1[N+](=O)[O-]
Agent: Cl[Ni]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Product: COc1ccc(C(N[C@@H](C)c2ccccc2)c2ccc(F)cc2)cc1N
Yield: 94.6 %

Procedure:
In a similar manner to that described in Example (1b), isomer A of N-[(4-methoxy-3-nitrophenyl)-(4-fluorophenyl)methyl]-N-[(S)-1-phenylethyl]amine (670 mg) [prepared as described in step (a) above], nickel chloride hexahydrate (856 mg) and sodium borohydride (272 mg) were reacted, to afford isomer A (584 mg) of the title compound as a yellow oil.
Reaction SMILES: C[CH:2]([CH:6]1[C:10]2=[CH:11][C:12]3[C:13]([CH:19]([CH3:21])[CH3:20])=[CH:14][C:15]([F:18])=[CH:16][C:17]=3[N:9]2[CH2:8][CH2:7]1)[C:3]([O-:5])=[O:4].[C:22]1([C:32](Cl)=[O:33])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1>>[F:18][C:15]1[CH:14]=[C:13]([CH:19]([CH3:21])[CH3:20])[C:12]2[C:11]([C:32]([C:22]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=[CH:24][CH:23]=3)=[O:33])=[C:10]3[CH:6]([CH2:2][C:3]([OH:5])=[O:4])[CH2:7][CH2:8][N:9]3[C:17]=2[CH:16]=1
Reactant: O=C(Cl)c1cccc2ccccc12
Reactant: CC(C)c1cc(F)cc2c1cc1n2CCC1C(C)C(=O)[O-]
Product: CC(C)c1cc(F)cc2c1c(C(=O)c1cccc3ccccc13)c1n2CCC1CC(=O)O

Procedure:
Starting from methyl(6-fluoro-8-isopropyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (Example 44, Step 2) and 1-naphthoyl chloride, the title compound was synthesized following the procedures described in Step 1 of Example 61 and Step 10 of Example 7.
Reaction SMILES: [C:1]([CH2:4][C:5]1[CH:13]=[CH:12][C:11]([Br:14])=[CH:10][C:6]=1[C:7]([OH:9])=[O:8])(O)=[O:2].C(Cl)(=O)C>CC(C)=O>[Br:14][C:11]1[CH:10]=[C:6]2[C:5]([CH2:4][C:1](=[O:2])[O:8][C:7]2=[O:9])=[CH:13][CH:12]=1
Reactant: O=C(O)Cc1ccc(Br)cc1C(=O)O
Solvent: CC(=O)Cl
Solvent: CC(C)=O
Product: O=C1Cc2ccc(Br)cc2C(=O)O1
Temperature: 25 °C
Reaction time: 18 h
Yield: 99.8 %

Procedure:
To a suspension of 2-(carboxymethyl)-5-bromobenzoic acid (2.37 g) in acetone (20 ml) was added acetyl chloride (2.60 ml) and the reaction mixture was stirred at room temperature for 18 hours. The solvent was evaporated and azeotroped with toluene (×3). The resultant solid was triturated with diethyl ether to yield 7-bromo-1H-isochromene-1,3(4H)-dione as a brown solid (2.20 g); NMR Spectrum: (DMSOd6) 4.24 (s, 2H), 7.42 (d, 1H), 7.94 (d, 1H), 8.13 (s, 1H).
Reaction SMILES: [N+](C1C=CC=CC=1N=NC1C=C(C)C=CC=1O)([O-])=O.[N+:20]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[N:29]=[N:30][C:31]1[CH:36]=[C:35]([C:37]([CH2:40][CH3:41])([CH3:39])[CH3:38])[CH:34]=[C:33]([C:42]([CH2:45][CH3:46])([CH3:44])[CH3:43])[C:32]=1[OH:47])([O-])=O.[OH-].[Na+].[OH-].[K+].CCCCCCCC/C=C\CCCCCCCC(OCC(O)[C@H]1OC[C@H](O)[C@H]1O)=O.CCCCCCCC/C=C\CCCCCCCC(OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O)=O.[H][H]>>[OH:47][C:32]1[C:33]([C:42]([CH2:45][CH3:46])([CH3:44])[CH3:43])=[CH:34][C:35]([C:37]([CH2:40][CH3:41])([CH3:39])[CH3:38])=[CH:36][C:31]=1[N:30]1[N:29]=[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]2=[N:20]1
Reactant: [H][H]
Reactant: CCC(C)(C)c1cc(N=Nc2ccccc2[N+](=O)[O-])c(O)c(C(C)(C)CC)c1
Agent: CCCCCCCC/C=C\CCCCCCCC(=O)OCC(O)[C@H]1OC[C@H](O)[C@H]1O
Agent: CCCCCCCC/C=C\CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O
Agent: Cc1ccc(O)c(N=Nc2ccccc2[N+](=O)[O-])c1
Product: CCC(C)(C)c1cc(-n2nc3ccccc3n2)c(O)c(C(C)(C)CC)c1
Yield: 71.9 %

Procedure:
When using the general procedure of Example 5, the 2-nitro-2'-hydroxy-5'-methylazobenzene was replaced by an equivalent amount of 2-nitro-2'-hydroxy-3',5'-di-tert-amylazobenzene and the sodium hydroxide was replaced by an equivalent amount of potassium hydroxide, the hydrogenation was run in an Amsco mineral spirits/water (40/60) medium containing 1% sorbitan monooleate, Span 80, wetting agent at a hydrogen pressure of 6 atmospheres for a total period of 8 hours. The above named product was obtained in an isolated yield of 71.9%.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][CH:6]([CH3:14])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])C.[H-].[Al+3].[Li+].[H-].[H-].[H-].S(=O)(=O)(O)O>CCOCC>[CH3:14][CH:6]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH2:5][CH2:4][OH:3]
Reactant: CCCCCCCC(C)CC(=O)OCC
Agent: O=S(=O)(O)O
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: CCCCCCCC(C)CCO
Yield: 88.8 %

Procedure:
740 g (3.46 mols) 3-methyl-decanoic acid ethyl ester, dissolved in 600 ml ether, are added while cooling to a suspension of 72 g (1.89 mols) lithium aluminium hydride in 600 ml ether. After the addition has ended the reaction mixture is heated for one hour to reflux temperature, is then hydrolysed and acidified with sulphuric acid. The organic phase is separated off, the aqueous phase is extracted with ether and the combined organic phases are freed from solvent. The destillation of the residue gives 529.5 g 3-methyldecanol (b.p.0.3 :83° C.), corresponding to a yield of 88.9% of theory.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[NH:15][C:16]1[N:20]([CH2:21][CH:22]([OH:28])[CH2:23][C:24](OC)=[O:25])[C:19]2[C:29]([N:33]([CH2:36][CH3:37])[CH2:34][CH3:35])=[CH:30][CH:31]=[CH:32][C:18]=2[N:17]=1.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1>[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[NH:15][C:16]1[N:20]([CH2:21][CH:22]([OH:28])[CH2:23][CH2:24][OH:25])[C:19]2[C:29]([N:33]([CH2:36][CH3:37])[CH2:34][CH3:35])=[CH:30][CH:31]=[CH:32][C:18]=2[N:17]=1
Reactant: CCN(CC)c1cccc2nc(Nc3ccc(Cl)cc3Cl)n(CC(O)CC(=O)OC)c12
Agent: O=S(=O)([O-])[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: C1CCOC1
Product: CCN(CC)c1cccc2nc(Nc3ccc(Cl)cc3Cl)n(CC(O)CCO)c12
Yield: 96.3 %

Procedure:
To a suspension of lithium aluminum hydride (15.9 mg, 0.429 mmol) in tetrahydrofuran (1 mL) was added a solution of methyl 4-[2-[(2,4-dichlorophenyl)amino]-7-(diethylamino)-1H-benzimidazol-1-yl]-3-hydroxybutanoate (Reference Example 83; 50.0 mg, 0.107 mmol) in tetrahydrofuran (1 mL) at 0° C. and the resultant mixture was stirred at 0° C. for 10 min. After sodium sulfate decahydrate (500 mg) was added at 0° C., the resultant mixture was filtered and concentrated in vacuo to give the title compound as an oil (45.0 mg, 0.103 mmol, 96%).
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:12]=[CH:13][C:14]=1[C:15]1[NH:19][N:18]=[CH:17][C:16]=1[CH:20]([CH3:25])[C:21]([NH:23][NH2:24])=[O:22])C1C=CC=CC=1>C(O)(C)C.[Pd]>[OH:8][C:9]1[CH:10]=[C:11]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:12]=[CH:13][C:14]=1[C:15]1[NH:19][N:18]=[CH:17][C:16]=1[CH:20]([CH3:25])[C:21]([NH:23][NH2:24])=[O:22]
Reactant: CC(C(=O)NN)c1cn[nH]c1-c1ccc(-c2ccccc2)cc1OCc1ccccc1
Agent: [Pd]
Solvent: CC(C)O
Product: CC(C(=O)NN)c1cn[nH]c1-c1ccc(-c2ccccc2)cc1O
Reaction time: 12 h

Procedure:
3 g of 5-(3-benzyloxy-1,1'-biphenyl-4-yl)-1H-pyrazol-4-yl-propionic acid hydrazide are dissolved with heating in isopropanol and hydrogenated over 10% palladium/charcoal. The catalyst is filtered off, the reaction mixture concentrated by evaporation and the concentrate allowed to stand for ca. 12 hrs. in a refrigerator. The title compound crystallises out as the dihydrochloride and is recovered by filtration: m.p.=138°-141° C.