Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[NH:13][C:12](=[O:14])[N:11]([C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21]C)=O)=[C:17]([O:25][CH3:26])[CH:16]=2)[N:10]=1.[Cl:27][C:28]1[CH:37]=[CH:36][C:31]([C:32](=[N:34]O)[NH2:33])=[CH:30][CH:29]=1.[H-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[NH:13][C:12](=[O:14])[N:11]([C:15]2[CH:24]=[CH:23][C:18]([C:19]3[O:21][N:34]=[C:32]([C:31]4[CH:36]=[CH:37][C:28]([Cl:27])=[CH:29][CH:30]=4)[N:33]=3)=[C:17]([O:25][CH3:26])[CH:16]=2)[N:10]=1
Reactant: NC(=NO)c1ccc(Cl)cc1
Reactant: COC(=O)c1ccc(-n2nc(-c3c(C)cccc3Cl)[nH]c2=O)cc1OC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cc(-n2nc(-c3c(C)cccc3Cl)[nH]c2=O)ccc1-c1nc(-c2ccc(Cl)cc2)no1
Yield: 15.6 %

Procedure:
The title compound was prepared by following the procedure as described for Example-40 by using methyl 4-(3-(2-chloro-6-methylphenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate (Intermediate-27, 0.100 g, 0.26 mmol), 4-chloro-N′-hydroxybenzimidamide (Intermediate-19, 0.069 g, 0.40 mmol), sodium hydride (0.022 g, 0.53 mmol) and dry THF (5.0 mL) to afford 0.020 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 2.33 (s, 3H), 4.00 (s, 3H), 7.41 (m, 1H), 7.51 (s, 2H), 7.67 (d, J=8.7 Hz, 2H), 7.83 (d, J=8.7 Hz, 1H), 7.90 (s, 1H), 8.10 (d, J=8.4 Hz, 2H), 8.22 (d, J=8.7 Hz, 1H), 12.63 (s, 1H); MS (m/z): 495.98 (M+H+).
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].Cl.[C:6]([C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=1)[CH2:12][NH2:13])(=[O:8])[CH3:7].C(N(CC)CC)C>ClCCl>[C:1]([NH:13][CH2:12][C:11]1[CH:10]=[C:9]([C:6](=[O:8])[CH3:7])[CH:16]=[CH:15][CH:14]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1cccc(CN)c1
Reactant: CC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)NCc1cccc(C(C)=O)c1
Temperature: 25 °C
Reaction time: 10 h
Yield: 62.1 %

Procedure:
Acetyl chloride (2.5 g) was added slowly to a suspension of 3-acetylbenzylamine hydrochloride (5.0 g) and triethylamine (6.0 g) in dichloromethane (50 ml) with cooling on an ice-water bath. The mixture was stirred at room temperature for 10 hours. The solvent was removed under reduced pressure. The residue was dissolved in water (100 ml). The solution was alkalified with an aqueous potassium carbonate solution. The mixture was extracted with ethyl acetate (150 ml). The solution was dried with magnesium sulfate. The solvent was removed under reduced pressure to afford 3'-acetylaminomethylacetophenone (3.2 g) (oil).
Reaction SMILES: [OH-].[Na+].[CH:3]1([CH2:6][O:7][C@@H:8]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([N:26]([CH3:37])[C:27]([NH:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:28])[CH:21]=3)=[CH:16][CH:15]=2)[C:9]([O:11]C)=[O:10])[CH2:5][CH2:4]1.O1CCCC1.CO.O>C(O)(=O)C>[CH:3]1([CH2:6][O:7][C@@H:8]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([N:26]([CH3:37])[C:27]([NH:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:28])[CH:21]=3)=[CH:16][CH:15]=2)[C:9]([OH:11])=[O:10])[CH2:5][CH2:4]1
Reactant: CCCCCCCNC(=O)N(C)c1cccc(-c2ccc(C[C@H](OCC3CC3)C(=O)OC)cc2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Solvent: C1CCOC1
Product: CCCCCCCNC(=O)N(C)c1cccc(-c2ccc(C[C@H](OCC3CC3)C(=O)O)cc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.3 %

Procedure:
21 mg (0.54 mmol) of sodium hydroxide are added to a solution of 86 mg (0.18 mmol) of methyl (S)-2-cyclopropylmethoxy-3-[3′-(3-heptyl-1-methylureido)biphenyl-4-yl]propionate in 2 ml of 9/1 tetrahydrofuran/methanol. The reaction mixture is stirred at ambient temperature overnight. The reaction is halted by the addition of 2 ml of water and 0.5 ml of acetic acid, and then extraction is carried out with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated and then the residue is chromatographed on silica gel (dichloromethane/methanol 90/10). 70 mg of 2(S)-cyclopropylmethoxy-3-[3′-(3-heptyl-1-methylureido)biphenyl-4-yl]propanoic acid are obtained in the form of an oil. Yield=84%.
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:13]=[C:12]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH:11]=[C:6]([C:7](OC)=[O:8])[CH:5]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>CCOCC>[CH2:15]([O:14][C:12]1[CH:11]=[C:6]([CH2:7][OH:8])[CH:5]=[C:4]([CH2:3][OH:2])[CH:13]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCCCCCCCCCCCOc1cc(C(=O)OC)cc(C(=O)OC)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: CCCCCCCCCCCCCCCCOc1cc(CO)cc(CO)c1
Yield: 37.5 %

Procedure:
The product was generated using general protocol E using dimethyl-5-hexadecyloxyisophthalate (D10, 6.30 g), lithium aluminum hydride (1.27 g, 33.5 mmol), Et2O (150 mL) yielded 2.06 g (37.9%) of a white solid. 1H NMR (CDCl3, 400 MHz) δ: 6.93 (s, 1H, Ar—H), 6.85 (s, 2H, Ar—H), 4.67 (d, 3J=5.9 Hz, 4H, Ar—CH2—OH), 3.97 (t, 6.4 Hz, 2H, O—CH2), 1.78 (p, 3J=7.6 Hz, 2H, OCH2CH2), 1.66 (t, 3J=6.0 Hz, 2H, CH2—OH), 1.45 (p, 3J=7.6 Hz, 2H, O CH2CH2CH2), 1.26 (m, 24H), 0.88 (t, 3J=6.6, 3H, CH2—CH3).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])[C:5]([N+:14]([O-])=O)=[CH:4][N:3]=1.[Sn](Cl)Cl.Cl>CCO>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])[C:5]([NH2:14])=[CH:4][N:3]=1
Reactant: CCC(CC)Nc1nc(Cl)ncc1[N+](=O)[O-]
Agent: Cl
Agent: Cl[Sn]Cl
Solvent: CCO
Product: CCC(CC)Nc1nc(Cl)ncc1N
Temperature: 80 °C

Procedure:
To a solution of (2-Chloro-5-nitro-pyrimidin-4-yl)-(1-ethyl-propyl)-amine (1 g, 4.087 mmol) in anhydrous EtOH (50 ml) is added Tin(II) chloride (2.324 g, 12.2607 mmol) and concentrated HCl (1 ml) at ambient temperature. The reaction is heated to 80° C. for 1 h and quenched with 1N NaOH at 0° C. The mixture is extracted with EtOAc, washed with brine, dried over Na2SO4, and concentrated in vacuo to give the crude product. The crude is used as is.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([NH:26][C:27]([NH:29][C@@H:30]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C@H:33]([O:40][C:41]3[CH:42]=[CH:43][C:44]4[N:45]([C:47]([N:50]5[CH2:55][CH2:54][O:53][CH2:52][C@@H:51]5[CH3:56])=[N:48][N:49]=4)[CH:46]=3)[CH2:32][CH2:31]2)=[O:28])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH2:17][CH2:18][O:19]C3CCCCO3)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.O.C([O-])(O)=O.[Na+]>CO>[C:1]([C:5]1[CH:6]=[C:7]([NH:26][C:27]([NH:29][C@@H:30]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C@H:33]([O:40][C:41]3[CH:42]=[CH:43][C:44]4[N:45]([C:47]([N:50]5[CH2:55][CH2:54][O:53][CH2:52][C@@H:51]5[CH3:56])=[N:48][N:49]=4)[CH:46]=3)[CH2:32][CH2:31]2)=[O:28])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH2:17][CH2:18][OH:19])[CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: C[C@H]1COCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(OCCOC5CCCCO5)c4)c4ccccc43)cn12
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CO
Product: C[C@H]1COCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(OCCO)c4)c4ccccc43)cn12
Temperature: 60 °C
Yield: 69.2 %

Procedure:
To a solution of Intermediate 141a (214 mg, 0.28 mmol) in MeOH (3.0 mL) was added pyridinium p-toluenesulfonate (141 mg, 0.56 mmol) and the reaction mixture was heated at 60° C. for 3 h. The resultant mixture was poured into water and a saturated aqueous solution of NaHCO3 was added. The aqueous phase was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 0-10% MeOH in DCM, to give the title compound (132 mg, 69%). LCMS (Method 4): Rt 3.04 min, m/z 681 [MH+].
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]=[O:11].[CH2:12]([Mg]Br)[CH3:13]>C1COCC1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([OH:11])[CH2:12][CH3:13]
Reactant: O=Cc1nc2ccccc2s1
Reactant: CC[Mg]Br
Solvent: C1CCOC1
Product: CCC(O)c1nc2ccccc2s1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 1,3-benzothiazole-2-carbaldehyde (0.96 g, 5.88 mmol) in THF (15.0 mL) was added ethylmagnesium bromide (1.0 M solution in THF, 12.0 mL, 12.0 mmol, 2 eq), slowly over 15 minutes (an exotherm was observed). The resulting dark red solution was stirred at room temperature for 55 minutes, then quenched with saturated aqueous ammonium chloride solution (4 mL). The mixture was then concentrated under reduced pressure. Purification by flash chromatography on silica gel (0-70% EtOAc in hexanes gradient) provided the title compound as a red oil.
Reaction SMILES: FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:29][CH2:28][N:18]2[C:19]3[CH:20]=[C:21]([S:26][CH3:27])[CH:22]=[CH:23][C:24]=3[CH2:25][CH:17]2[CH2:16]1)=O)(C)(C)C.C(=O)([O-])O.[Na+].[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39]>ClCCl.CC(O)C>[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39].[CH3:27][S:26][C:21]1[CH:22]=[CH:23][C:24]2[CH2:25][CH:17]3[CH2:16][NH:15][CH2:29][CH2:28][N:18]3[C:19]=2[CH:20]=1
Reactant: CSc1ccc2c(c1)N1CCN(C(=O)OC(C)(C)C)CC1C2
Agent: O=C(O)/C=C/C(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(C)O
Solvent: O=C(O)C(F)(F)F
Product: CSc1ccc2c(c1)N1CCNCC1C2
Temperature: 25 °C
Reaction time: 1 h
Yield: 54 %

Procedure:
Trifluoroacetic acid (1 mL) was added to a stirred solution of 2-tert-butoxycarbonyl-7-(methylthio)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole (70 mg, 0.21 mmol) in dichloromethane. (5 mL) at room temperature under Ar. The reaction was stirred at room temperature for 1 h then poured into saturated aqueous sodium hydrogen carbonate solution (50 mL) and extracted with dichloromethane (3×30 mL). The combined organic extracts, were washed with brine (1×30 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude oil. The oil was dissolved in 2-propanol (5 mL) and heated to reflux. Fumaric acid (1 eq) was added and the solution was cooled to room temperature. The emerging precipitate was filtered, washed with ether and dried to give the product as a white solid (40 mg, 54%). mp 196–198° C. Found: C, 56.50; H, 5.89; N, 8.15%. C12H16N2S. 1.1 C4H4O4 requires: C, 56.60; H, 5.91; N, 8.05%. IR νmax (Nujol)/cm−1 3595, 3188, 2925, 2854, 2457, 1696, 1585, 1485, 1486, 1461, 1402, 1377, 1345, 1317, 1279, 1230, 1179, 1154, 1129, 1066, 1058, 1005, 996, 972, 919, 987, 868, 835, 797, 722, 644, 606, 547 and 482: NMR δH (400 MHz; DMSO-d6) 6.99 (1H, d, J 7.5 Hz), 6.52 (2H, s), 6.47–6.51 (2H, m), 3.69–3.72 (1H, m), 3.50–3.62 (2H, m), 3.05–3.20 (3H, m), 2.91–3.02 (2H, m), 2.65–2.80 (2H, m), 2.43 (3H, s).
Reaction SMILES: Cl.COC1C=CC(C[NH:9][C:10]2[CH:15]=[C:14]([NH:16][CH2:17][CH2:18][O:19][CH3:20])[C:13]([C:21]([F:24])([F:23])[F:22])=[CH:12][N:11]=2)=CC=1.C([O-])(O)=O.[Na+]>>[CH3:20][O:19][CH2:18][CH2:17][NH:16][C:14]1[C:13]([C:21]([F:24])([F:22])[F:23])=[CH:12][N:11]=[C:10]([NH2:9])[CH:15]=1
Reactant: COCCNc1cc(NCc2ccc(OC)cc2)ncc1C(F)(F)F
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: COCCNc1cc(N)ncc1C(F)(F)F
Reaction time: 4.5 h

Procedure:
Concentrated hydrochloric acid (1.5 ml) was added to N2-(4-methoxybenzyl)-N4-(2-methoxyethyl)-5-(trifluoromethyl)pyridine-2,4-diamine (intermediate 85, 280 mg, 0.788 mmol) at room temperature. After stirring for 4.5 h the reaction mixture was neutralised with saturated aqueous NaHCO3 solution, extracted with DCM (4×), dried over Na2SO4 and evaporated. The residue was applied to a 12 g RediSep® silica column as a DCM solution and purified by normal phase chromatography, eluting with a gradient from DCM to 10% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 5.68 (s, 1H), 4.95 (s, br, 1H), 4.50 (s, br, 2H), 3.62-3.57 (m, 2H), 3.38 (s, 3H), 3.30-3.25 (m, 2H). (UPLC-MS 6) tR 0.44; ESI-MS 236.1 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([NH2:12])=[C:7]([Cl:13])[CH:6]=[CH:5][C:4]=2[N:3]=1.[F:14][C:15]([F:27])([F:26])[CH:16]1[CH2:21][CH2:20][CH:19]([CH2:22][C:23](O)=[O:24])[CH2:18][CH2:17]1>>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:13])[C:8]=2[NH:12][C:23](=[O:24])[CH2:22][CH:19]2[CH2:18][CH2:17][CH:16]([C:15]([F:26])([F:14])[F:27])[CH2:21][CH2:20]2)[N:3]=1
Reactant: Nc1c(Cl)ccc2nc(Cl)ccc12
Reactant: O=C(O)CC1CCC(C(F)(F)F)CC1
Product: O=C(CC1CCC(C(F)(F)F)CC1)Nc1c(Cl)ccc2nc(Cl)ccc12
Yield: 46 %

Procedure:
Prepared according to the method of example 1(a), using 2,6-dichloroquinolin-5-amine (prepared as described in Example 1(d) above) (400 mg) and 4-(trifluoromethyl)-cyclohexaneacetic acid (Example 8 (b)) (436 mg). Purification (SiO2, dichloromethane:methanol 99:1 as eluant) gave the sub-title compound (350 mg).
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].F[C:15]1[CH:16]=[C:17]([O:30][CH2:31][C:32]([F:35])([F:34])[F:33])[C:18]([N+:27]([O-:29])=[O:28])=[C:19]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])[CH:20]=1.O>CN(C=O)C>[CH2:10]([O:9][C:1](=[O:8])[CH:2]([C:15]1[CH:16]=[C:17]([O:30][CH2:31][C:32]([F:34])([F:35])[F:33])[C:18]([N+:27]([O-:29])=[O:28])=[C:19]([O:21][CH2:22][C:23]([F:24])([F:26])[F:25])[CH:20]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:11]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: O=[N+]([O-])c1c(OCC(F)(F)F)cc(F)cc1OCC(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)C(C(=O)OCC)c1cc(OCC(F)(F)F)c([N+](=O)[O-])c(OCC(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 81.6 %

Procedure:
To a solution of diethyl malonate (18.0 g, 114.9 mmol) in DMF (50 mL) was added sodium hydride (60% in mineral oil, 3.0 g, 125.0 mmol) at 0° C. The reaction mixture was stirred at 25° C. for 0.5 h and a solution of 5-fluoro-2-nitro-1,3-bis-(2,2,2-trifluoro-ethoxy)-benzene (18.0 g, 53.4 mmol) in DMF (30 mL) was added dropwise. The reaction mixture was heated 100° C. for 24 h. After cooling the reaction mixture was poured into water (300 mL) and extracted with EtOAc (3×50 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of the solvent under reduced pressure gave 2-[4-nitro-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-malonic acid diethyl ester as a brown oil (20.8 g, 80%). The crude product was used for the next step without purification. 1H NMR (300 MHz, CDCl3/TMS): δ 6.91 (s, 2H), 4.62 (s, 1H), 4.48 (q, J=8.0 Hz, 4H), 4.28-4.16 (m, 4H), 1.31-1.25 (m, 6H). 13C NMR (75 MHz, CDCl3/TMS): δ 166.4, 149.2, 136.7, 132.3, 122.3 (q, 1JCF=276.6 Hz), 109.5 (two signals), 67.0 (q, 2JCF=36.7 Hz), 61.4, 41.6, 14.0.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[C:5](Cl)(=[O:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:14]1([CH:20]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])[C:21]([OH:23])=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(Cl)(Cl)(Cl)Cl>[C:5]([C:20]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])[C:21]([OH:23])=[O:22])(=[O:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CCCCCCCCCCCCCCCCC(C(=O)O)c1ccccc1
Reactant: O=C(Cl)c1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClC(Cl)(Cl)Cl
Product: CCCCCCCCCCCCCCCCC(C(=O)O)(C(=O)c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 40.4 %

Procedure:
To a one-liter glass reactor equipped with a mechanical stirrer, condenser, thermometer and addition funnel was charged 300 mls freshly distilled carbon tetrachloride. The flask and its contents were cooled to 0°-5° C. and 40 grams (0.30 mole) AlCl3 added slowly. This was followed by the dropwise addition of 42 grams (0.30 mole) benzoyl chloride and then 26.9 grams (0.075 mole) phenylstearic acid. The mixture was maintained at 0°-5° C. for one hour with agitation and then allowed to warm to room temperature and stirred overnight. A yield of 40.4 percent crude benzoylphenylstearic acid was obtained upon work up of the reaction mixture.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.Cl[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=2)[CH:14]=[C:13]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)[N:12]=1>>[CH3:29][C:27]1[NH:26][N:25]=[C:24]([NH:23][C:13]2[N:12]=[C:11]([O:1][C:2]3[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=3)[C:20]3[C:15]([CH:14]=2)=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=3)[CH:28]=1
Reactant: N#Cc1ccc(O)cc1
Reactant: COc1ccc2cc(Nc3cc(C)[nH]n3)nc(Cl)c2c1
Product: COc1ccc2cc(Nc3cc(C)[nH]n3)nc(Oc3ccc(C#N)cc3)c2c1

Procedure:
Similar procedure as described in example 10 was used, starting from 4-Hydroxy-benzonitrile and (1-chloro-7-methoxy-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine to give 4-[3-(5-methyl-1H-pyrazol-3-ylamino)-7-methoxy-isoquinolin-1-yloxy]-benzonitrile. LC-MS m/e 372(MH+).
Reaction SMILES: C(=O)(O[C:4]1([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)=[CH:20][CH:19]=2)[CH2:9][O:8]C(C)(C)[O:6][CH:5]1C(C)(C)C)N.C(OC(=O)[NH:38]C1(CCC2C=CC(S(N3C4C(=CC=C(OC)C=4)C(C(=O)C4C=C(OC)C(OC)=C(OC)C=4)=C3)(=O)=O)=CC=2)COC(C)(C)OC1)(C)(C)C>>[NH2:38][C:4]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)=[CH:20][CH:19]=1)([CH2:9][OH:8])[CH2:5][OH:6]
Reactant: Cc1ccc(-c2ccc(CCC3(OC(N)=O)COC(C)(C)OC3C(C)(C)C)cc2)cc1
Reactant: COc1ccc2c(C(=O)c3cc(OC)c(OC)c(OC)c3)cn(S(=O)(=O)c3ccc(CCC4(NC(=O)OC(C)(C)C)COC(C)(C)OC4)cc3)c2c1
Product: Cc1ccc(-c2ccc(CCC(N)(CO)CO)cc2)cc1
Yield: 67 %

Procedure:
When the product of Step A was substituted for tert-butyl-5-(4-(6-methoxy-3-(3,4,5-trimethoxybenzoyl)-1H-indol-1-ylsulfonyl)-phenethyl)-2,2-di methyl-1,3-dioxan-5-ylcarbamate in Example 13, Step F, the similar process afforded the title compound in 67% yield, as colourless solid. 1H-NMR (CDCl3) 3.17-3.23 (m, 2H); 3.63 (s, 3H); 3.94-3.88 (m, 2H); 4.91 (d, 2H, J=12.36 Hz); 4.97 (d, 2H, J=11.94 Hz); 8.12 (tr, 4H, J=10.92 Hz); 8.66-8.88 (m, 4H).
Reaction SMILES: [CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[S:20][C:19]3[C:18]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[N:17][C:16]([C:27]4[S:31][C:30]([NH2:32])=[N:29][CH:28]=4)=[N:15][C:14]=3[CH:13]=2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].C(N(CC)CC)C.[C:40](Cl)(=[O:42])[CH3:41]>C1COCC1>[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[S:20][C:19]3[C:18]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[N:17][C:16]([C:27]4[S:31][C:30]([NH:32][C:40](=[O:42])[CH3:41])=[N:29][CH:28]=4)=[N:15][C:14]=3[CH:13]=2)[CH2:7][CH2:6]1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)N1CCN(Cc2cc3nc(-c4cnc(N)s4)nc(N4CCOCC4)c3s2)CC1
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(=O)Nc1ncc(-c2nc(N3CCOCC3)c3sc(CN4CCN(S(C)(=O)=O)CC4)cc3n2)s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 54.2 %

Procedure:
To a solution of 5-[6-(4-methanesulphonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-2-yl]-thiazol-2-ylamine (12 mg, 0.024 mmol) in THF (1 ml) at RT triethylamine (8 ul, 0.053 mmol, 2 eq) and acetyl chloride (2 ul, 0.026 mmol, 1.1 eq) was added and the reaction allowed to stir at RT overnight. The solution was extracted into ethyl acetate (10 ml) washing with water (2×10 ml), and dried over MgSO4. The crude material was triturated with diethyl ether to give 401 as a yellow solid (7 mg, 54% yield). NMR (CDCl3, 400 MHz), 2.34 (3H, s), 2.69 (4H, t, J=4.8), 2.83 (3H, s), 3.22 (4H, t, J 4.8), 3.89-3.91 (6H, m), 4.03 (4H, t, J=4.8), 7.33 (1H, s), 8.23 (1H, s), 9.44 (1H, br s). MS: (ESI+): MH+=538
Reaction SMILES: [C:1]1([CH2:11][C:12]#[N:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Na].CO.[C:17](=O)([O:20]C)[O:18][CH3:19]>>[C:1]1([CH:11]([C:17]([O:18][CH3:19])=[O:20])[C:12]#[N:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)OC
Reactant: N#CCc1cccc2ccccc12
Agent: [Na]
Solvent: CO
Product: COC(=O)C(C#N)c1cccc2ccccc12

Procedure:
0.1 mol of 2-(1-naphthyl)acetonitrile is dissolved in 120 cm3 of dimethyl carbonate, and the solution is heated to reflux. 0.1 mol of sodium is then added in small portions over 30 min, during which time the methanol evaporates off. The reaction medium is kept refluxing for 1 hour, and the excess dimethyl carbonate is then evaporated off to dryness. The residue is taken up with 100 cm3 of an 18% solution of acetic acid in water.
Reaction SMILES: CNCCC(OC1C=CC(C(F)(F)F)=CC=1)C1C=CC=CC=1.Cl.[CH3:24][N:25]([CH3:36])[CH2:26][CH2:27][C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:29].B#B>>[CH3:24][N:25]([CH2:26][CH2:27][CH:28]([OH:29])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH3:36]
Reactant: CN(C)CCC(=O)c1ccccc1
Agent: B#B
Agent: CNCCC(Oc1ccc(C(F)(F)F)cc1)c1ccccc1
Agent: Cl
Product: CN(C)CCC(O)c1ccccc1

Procedure:
In the process for the preparation of fluoxetine, as in U.S. Pat. No. 4,314,081, β-dimethylaminopropiophenone hydrochloride is used as a starting material which, after the liberation of the base, is hydrogenated with diborane, B2H4. The N,N-dimethyl-3-hydroxy-3-phenylpropylamine produced in the reaction is allowed to react with thionyl chloride in chloroform containing hydrochloric acid yielding N,N-dimethyl-3-phenyl-3-chloropropylamine. This compound is allowed to react under alkaline conditions with p-trifluoro-methylphenol by heating the mixture under reflux for 5 days and nights, after which N,N-dimethyl-3-p-trifluoromethylphenoxy-3-phenylpropylamine is produced. This compound is N-demethylated with the aid of cyanogen bromide, yielding N-methyl-N-cyano-3-(p-trifuoromethylphenoxy)-phenylpropylamine. The N-cyano group is removed from this compound by heating for 20 hours at 130° C. under reflux in a mixture of potassium hydroxide and ethylene glycol. The reaction mixture is extracted with ether and the ether phase is evaporated to dryness. The residue could further be transformed in a known manner into a pharmaceutically acceptable salt of fluoxetine.
Reaction SMILES: B.[Na].[C:3]([C:7]1[C:12]([C:13](=[O:21])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])=[CH:11][N:10]=[CH:9][N:8]=1)([CH3:6])([CH3:5])[CH3:4]>CO>[C:3]([C:7]1[C:12]([CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[OH:21])=[CH:11][N:10]=[CH:9][N:8]=1)([CH3:6])([CH3:5])[CH3:4]
Reactant: Cc1ccccc1C(=O)c1cncnc1C(C)(C)C
Agent: B
Agent: [Na]
Solvent: CO
Product: Cc1ccccc1C(O)c1cncnc1C(C)(C)C
Reaction time: 2 h
Yield: 59.5 %

Procedure:
500 ml of sodium boron hydride (purity 92%) was added to a mixture of 1 g of 4-tert-butyl-5-(2-methylbenzoyl)pyrimidine and 20 ml of dry methanol, under cooling with ice, and the resulting mixture was stirred for 2 hours. The solvent was distilled off under reduced pressure, and to the resulting mixture, ice water and ethyl acetate were added, and the pH was adjusted to a level from 1 to 2 with concentrated hydrochloric acid with stirring. The organic layer was washed with saturated aqueous salt solution twice, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 600 mg of the desired product as white crystals.