Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:23])([C:7]3[CH:15]=[CH:14][C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([NH2:22])[CH:17]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:24].N1C=CC=CC=1.ClCCl.[C:34](Cl)(=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36]>C(Cl)(Cl)Cl>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:23])([C:7]3[CH:15]=[CH:14][C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][C:34](=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36])[CH:17]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:24]
Reactant: CN1C(=O)CC[C@]2(C)c3ccc(-c4cccc(N)c4)cc3CC[C@@H]12
Reactant: CC(C)(C)C(=O)Cl
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CN1C(=O)CC[C@]2(C)c3ccc(-c4cccc(NC(=O)C(C)(C)C)c4)cc3CC[C@@H]12
Temperature: 25 °C
Yield: 63.7 %

Procedure:
A 15 mL round bottom flask was charged with (+)-(4aR)(10bR)-4-methyl-8-(3-aminophenyl)-10b-methyl 1,2,3,4,4a,5,6,10b octahydrobenzo[f]quinolin-3-one (31 mg, 0.097 mmol), N,N-dimethylaminopyridine (3 mg, 0.024 mmol), 1 mL of pyridine and 0.5 mL of dichloromethane. The solution was cooled to 0°, and excess pivaloyl chloride (0.086 mL, 0.69 mmol) was added. The stirred mixture was allowed to warm to room temperature over 2 h. The mixture was diluted with chloroform, and washed with 5% aqueous hydrochloric acid solution, water, 5% queous sodium hydroxide solution, water, and the combined organic extracts were dried over sodium sulfate, concentrated and chromatographed on silica gel (ethyl acetate eluent) to give 25 mg (64%) of the title compound as a yellow solid. mp 95°-98°. FDMS m/e=404. α[D]589 =+62.50 (c=0.16, chloroform).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1B(O)O.C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C>C(COC)OC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCCCCC>[Cl:1][C:2]1[CH:7]=[C:6]([C:10]2[S:9][CH:13]=[CH:12][CH:11]=2)[N:5]=[CH:4][N:3]=1
Reactant: Clc1cc(Cl)ncn1
Reactant: OB(O)c1cccs1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: O
Solvent: COCCOC
Product: Clc1cc(-c2cccs2)ncn1
Yield: 62.8 %

Procedure:
4,6-dichloropyrimidine (22.2 g, 149.1 mmol), thiophene-2-boronic acid (20.0 g, 156.3 mmol, 1.05 equiv), Na2CO3 (28.8 g, 271.4 mmol, 1.8 equiv) and Pd(PPh3)2Cl2 (2.9 g, 4.2 mmol, 0.03 equiv) were refluxed in dimethoxyethane-water (727:238 mL) mixed solvent system for 16 h. Reaction was monitored by TLC (using ethyl acetate:n-hexane, 1:9). Reaction mixture was cooled and the subject compound was extracted using dichloromethane. Subject compound was purified by flash chromatography (5% ethyl acetate:n-hexane) to yield 18.4 g of 3 (Yield=62.8%).
Reaction SMILES: Cl[C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH3:16])=[C:6](Cl)[N:5]=[C:4]([C:18]([F:21])([F:20])[F:19])[N:3]=1.[C:22]([C:26]1[CH:31]=[CH:30][C:29]([S:32]([NH2:35])(=[O:34])=[O:33])=[CH:28][CH:27]=1)([CH3:25])([CH3:24])[CH3:23]>C1(C)C=CC=CC=1>[C:22]([C:26]1[CH:31]=[CH:30][C:29]([S:32]([NH:35][C:2]2[C:7]([O:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][CH3:16])=[C:6]([O:8][CH2:9][CH2:10][OH:15])[N:5]=[C:4]([C:18]([F:21])([F:20])[F:19])[N:3]=2)(=[O:33])=[O:34])=[CH:28][CH:27]=1)([CH3:25])([CH3:23])[CH3:24]
Reactant: COc1ccccc1Oc1c(Cl)nc(C(F)(F)F)nc1Cl
Reactant: CC(C)(C)c1ccc(S(N)(=O)=O)cc1
Solvent: Cc1ccccc1
Product: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(C(F)(F)F)nc1OCCO

Procedure:
By reacting 4,6-dichloro-5-(2-methoxyphenoxy)-2-trifluoromethylpyrimidine with p-tert-butylbenzenesulfonamide and with ethylene glycol Na there was obtained p-tert-butyl-N-[6-(2-hydroxyethoxy)-5(o-methoxyphenoxy)-2-(trifluoromethyl)-4-pyrimidinyl]benzenesulfonamide, m.p. 190°-192° C. (from toluene). Sodium salt: M.p. 288°-289° C.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]([F:20])([F:19])[C:9]1[C:14]([C:15](OC)=[O:16])=[CH:13][N:12]=[CH:11][CH:10]=1.C(OCC)(=O)C.O>C1COCC1>[F:19][C:8]([F:7])([F:20])[C:9]1[CH:10]=[CH:11][N:12]=[CH:13][C:14]=1[CH2:15][OH:16]
Reactant: COC(=O)c1cnccc1C(F)(F)F
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: OCc1cnccc1C(F)(F)F
Temperature: -50 °C
Reaction time: 3 h
Yield: 34.6 %

Procedure:
A solution of 0.37 g (9.7 mmoles) of lithium aluminum hydride dissolved in 100 ml of THF was cooled to −50° C. Thereto was gradually added dropwise a solution of 2.0 g (9.8 mmoles) of methyl 4-trifluoromethylnicotinate dissolved in 30 ml of THF. The mixture was stirred at −50° C. for 3 hours to give rise to a reaction. After confirmation of the completion of the reaction, ethyl acetate was added, followed by stirring for a while. Water was added, followed by stirring for a while. The reaction mixture was filtered under vacuum. The filtrate was extracted with ethyl acetate. The resulting organic layer was washed with water and an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to vacuum distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate mixed solvent) to obtain 0.6 g (yield: 35.3%) of (4-trifluoromethylpyridin-3-yl)-methanol as a yellow oily substance.
Reaction SMILES: C1(C[O:8][C:9]2[C:19]3[O:18][CH2:17][CH2:16][N:15]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:14][C:13]=3[CH:12]=[CH:11][CH:10]=2)C=CC=CC=1>C(O)C.[Pd]>[OH:8][C:9]1[C:19]2[O:18][CH2:17][CH2:16][N:15]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:14][C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: CC(C)(C)OC(=O)N1CCOc2c(cccc2OCc2ccccc2)C1
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCOc2c(O)cccc2C1
Yield: 100 %

Procedure:
A solution of 1,1-dimethylethyl 9-[(phenylmethyl)oxy]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (Preparation 61) (8.25 g, 23.21 mmol) in ethanol (100 ml) was hydrogenated with 10% palladium on carbon (0.825 g, 7.75 mmol) for 18 hours, filtered and evaporated to give 6.16 g of white solid. MS (ES−): C21H25NO4 requires 265; found 264 [M−H+].
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.C([Li])CCC.[CH2:14]([CH:19]1[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]1)[CH2:15][CH2:16][CH2:17][CH3:18].Cl>C1(C)C=CC=CC=1.CCCCCC>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:22]2[CH2:23][CH2:24][CH:19]([CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:20][CH:21]=2)=[CH:3][CH:4]=1
Reactant: CCCCCC1CCC(=O)CC1
Reactant: Brc1ccc(Br)cc1
Agent: Cl
Agent: [Li]CCCC
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: CCCCCC1CC=C(c2ccc(Br)cc2)CC1
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 65.1 %

Procedure:
236 Grams (1 mol) of p-dibromobenzene and 1 l of dry toluene were introduced into a three-neck flask in dry nitrogen atmosphere to carry out dissolution with stirring at 50° C. To the resulting solution was dropwise added 525 ml of a hexane solution of 1.67 N commercial n-butyllithium (0.88 mol), over 30 minutes. After dropping, the temperature was maintained at 50° C. further for 30 minutes, and then lowered down to 25° C. To this solution was dropwise added a solution obtained by dissolving 135 g (0.8 mol) of 4-n-pentylcyclohexanone in 125 ml of toluene, over 30 minutes, followed by continuing stirring for 30 minutes at 30° C., and then 250 ml of 6 N hydrochloric acid was added dropwise while maintaining the temperature at 30° C. or lower (the first step). The resulting organic layer was separated, 25 g of potassium hydrogen sulfate was added thereto, and after hexane was distilled off with stirring, the resulting residue was concentrated until the liquid temperature reached 110° C. to complete the dehydration reaction (the second step). The resulting concentrate was distilled under a reduced pressure to take a fraction of 160°~170° C./1 mm Hg, whereby there was obtained 160 g of 1-(p-bromophenyl)-4-n-pentylcyclohexene (R=n-C5H11 and n=1 in said formula (B)) (yield: 62.4%), which was then twice recrystallized from ethanol to give a crystal having a melting point of 67°~68° C.
Reaction SMILES: C(O[C:4](=[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[NH:13][C:12]1=[O:23])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)C.[N:24]1([CH2:30][C:31]2[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>CN(C=O)C>[N:24]1([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([NH:35]/[C:4](=[C:11]3\[C:12](=[O:23])[NH:13][C:14]4[C:19]\3=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=4)/[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)=[CH:36][CH:37]=2)[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1
Reactant: Nc1ccc(CN2CCCCC2)cc1
Reactant: CCOC(=C1C(=O)Nc2ccc([N+](=O)[O-])cc21)c1ccccc1
Solvent: CN(C)C=O
Product: O=C1Nc2ccc([N+](=O)[O-])cc2/C1=C(/Nc1ccc(CN2CCCCC2)cc1)c1ccccc1

Procedure:
Prepared analogously to Example 89 from 3-(1-ethoxy-1-phenyl-methylidene)-5-nitro-2-indolinone and 4-piperidinomethyl-aniline in DMF.
Reaction SMILES: [BH4-].[Na+].[C:3]([C:6]1[C:10]([Cl:11])=[C:9]([C:12]([NH:14][C@@H:15]([CH3:31])[CH2:16][N:17]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[C:24]([Cl:30])[CH:23]=3)=[N:18]2)=[O:13])[NH:8][N:7]=1)(=[O:5])[CH3:4].[Cl-].[NH4+]>C(O)C>[Cl:11][C:10]1[C:6]([CH:3]([OH:5])[CH3:4])=[N:7][NH:8][C:9]=1[C:12]([NH:14][C@@H:15]([CH3:31])[CH2:16][N:17]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[C:24]([Cl:30])[CH:23]=2)=[N:18]1)=[O:13]
Reactant: CC(=O)c1n[nH]c(C(=O)N[C@@H](C)Cn2ccc(-c3ccc(C#N)c(Cl)c3)n2)c1Cl
Agent: [BH4-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Product: CC(O)c1n[nH]c(C(=O)N[C@@H](C)Cn2ccc(-c3ccc(C#N)c(Cl)c3)n2)c1Cl
Temperature: 50 °C
Reaction time: 19 h
Yield: 45.6 %

Procedure:
Into a mixture containing sodium borohydride (0.044 g, 1.159 mmol) in ethanol (10 ml), (S)-3-acetyl-4-chloro-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-5-carboxamide (0.5 g, 1.159 mmol) of Example 314 was slowly added and the temperature was raised to 50° C. for 10 min. The reaction mixture was stirred at RT for 19 h. Saturated ammonium chloride (30 ml) was added and the mixture was extracted with ethyl acetate, combined organic layers dried with Na2SO4, filtered and evaporated. The product was purified with flash chromatography. Yield 45.6%. 1H-NMR (400 MHz; CDCl3): δ 1.24 (d, 3H), 1.58 (dd, 3H), 2.88 (bs, 1H), 4.25-4.32 (m, 1H), 4.41-4.49 (m, HA), 4.56-4.68 (m, 1H), 5.04-5.12 (m, 1H), 6.62 (d, 1H), 7.48-7.51 (m, 1H), 7.61-7.67 (m, 2H), 7.70-7.75 (m, 1H), 8.01-8.07 (m, 1H), 11.27 (bs, 1H).
Reaction SMILES: CCN(C(C)C)C(C)C.[C:10]1([CH2:16][C:17]([O:19][CH2:20]C)=[O:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.O(C1CCCC1)S(C(F)(F)F)(=O)=O.[CH3:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40].COC(C)(C)C>C1COCC1.CN1C(=O)N(C)CCC1>[CH3:20][O:19][C:17](=[O:18])[CH:16]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH2:35][CH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1
Reactant: CCOC(=O)Cc1ccccc1
Reactant: CCCCCC
Agent: O=S(=O)(OC1CCCC1)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN1CCCN(C)C1=O
Solvent: C1CCOC1
Product: COC(=O)C(CC1CCCC1)c1ccccc1
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
To a 500 mL round bottom flask containing 250 mL of 9:1 THF/DMPU at −78° C. is added 17 mL DIEA followed by rapid addition of 49 mL of 2.5 M n-BuLi/hexanes. After 10 min at −78° C., a solution of ethyl phenylacetate (17.0 g, 113 mmol) in 50 mL of 9:1 THF/DMPU is added dropwise over 15-20 min. A yellow solution results, and the reaction mixture is stirred at −78° C. for 30-45 min. A solution of 26.7 g (115 mmol) of freshly prepared cyclopentyl triflate (title B compound in Example 1) in 25 mL 9:1 THF/DMPU is added dropwise over 10-15 min. The mixture is then stirred over 2-3 h to ambient temperature. The reaction is quenched into 300 mL of 1 N HCl and extracted 3 times with methyl-t-butylether (MTBE). The combined extracts are washed with saturated NaCl and dried over anhydrous magnesium sulfate. Filtration and evaporation afford crude product as a yellow oil. Flash chromatography over silica gel eluting with 4:1 hexane/MTBE affords 3-cyclopentyl-2-phenylpropionic acid methyl ester as a light yellow oil: 1H NMR (400 MHz, CDCl3) δ 1.1 (m, 2H), 1.3 (m, 1H), 1.50 (m, 2H), 1.6 (m, 2H), 1.7 (m, 2H), 2.1(dt, J=13.4, 7.7 Hz, 1H), 3.60 (m, 1H), 3.64 (s, 3H), 7.3 (m, 5H); LC/MS 233 (M+1).
Reaction SMILES: [CH:1](=O)[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]([O:14]C(=O)C)(=[O:13])[CH3:12].C([O-])(=O)C.[K+].C([O-])(=O)C.[Na+]>C(O)(=O)C.C(OC(=O)C)(=O)C>[C:4]1([CH:3]=[CH:2][CH:1]=[CH:12][C:11]([OH:14])=[O:13])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CC(=O)OC(C)=O
Reactant: O=CC=Cc1ccccc1
Agent: CC(=O)[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CC(=O)O
Product: O=C(O)C=CC=Cc1ccccc1
Temperature: 25 °C

Procedure:
Into a one liter round bottom flask equipped with a stirrer, condenser, thermometer and heating mantle, 198 grams (1.5 mols) of cinnamaldehyde, 230 grams (2.25 mols) of acetic anhydride, 25 grams (0.25 mols) potassium acetate, and 49 grams (0.60 mols) of sodium acetate were charged. The contents were brought up to 145° C. and maintained at 145°-150° C. for ninety minutes. Approximately 100 ml of acetic acid/acetic anhydride were stripped off leaving a red brown slurry. The resultant slurry was cooled to room temperature and the solids filtered off and rinsed with acetone. The dry filtercake (185 grams) was dissolved in two liters of 5% potassium carbonate solution at 65° C. Addition of 100 ml of 37.8% HCl to this solution yielded 5-phenyl-2,4-pentadienoic acid as a light yellow precipitate. The precipitate was filtered and dried. The dried acid was esterified with ethanol in the presence of sulfuric acid. The resultant ethyl 5-phenyl-2,4-pentadienoate was purified by vacuum distillation. The pure product was found to have a max of 309 nm, and an extinction coefficient of 35,500.
Reaction SMILES: [NH2:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][C:3]=1[F:15].[F:16][C:17]1[CH:18]=[CH:19][C:20]([CH3:26])=[C:21]([N:23]=[C:24]=S)[CH:22]=1>CO>[F:16][C:17]1[CH:18]=[CH:19][C:20]([CH3:26])=[C:21]([NH:23][C:24]2[O:8][C:7]3[CH:6]=[C:5]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:4]=[C:3]([F:15])[C:2]=3[N:1]=2)[CH:22]=1
Reactant: CCOC(=O)Cc1cc(O)c(N)c(F)c1
Reactant: Cc1ccc(F)cc1N=C=S
Solvent: CO
Product: CCOC(=O)Cc1cc(F)c2nc(Nc3cc(F)ccc3C)oc2c1
Temperature: 25 °C
Yield: 56.7 %

Procedure:
Under stirring at room temperature, ethyl 4-amino-3-fluoro-5-hydroxyphenylacetate (233 mg, 1.10 mmol) was added to a solution of 5-fluoro-2-methylphenyl isothiocyanate (184 mg, 1.10 mmol) in methanol (20 ml). The resulting mixture was stirred at 70° C. for 1 hour. To the reaction mixture was added mercuric oxide (yellow) (262 mg, 1.21 mmol), followed by stirring for further 30 minutes. After cooling to room temperature, the reaction mixture was filtered through Celite. The filtrate was washed with methanol and then, distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from chloroform/methanol (10/1) eluate fractions, ethyl (2-(5-fluoro-2-methylphenylamino)-4-fluoro-6-benzoxazolyl)acetate (216 mg, 57%) was obtained as a pale yellow solid.
Reaction SMILES: [CH3:1][C:2]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[NH:6][C:5](=[O:7])[NH:4][C:3]1=[O:8].C(=O)([O-])[O-].[K+].[K+].I[CH:22]([CH3:24])[CH3:23]>CN(C=O)C>[CH:22]([N:4]1[C:3](=[O:8])[C:2]([CH3:1])([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:6][C:5]1=[O:7])([CH3:24])[CH3:23]
Reactant: CC(C)I
Reactant: CC1(c2ccccc2)NC(=O)NC1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)N1C(=O)NC(C)(c2ccccc2)C1=O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred solution of (±)-5-methyl-5-phenylhydantoin (3.0 g, 15.7 mmol) in DMF (20 mL) was added potassium carbonate (2.6 g, 18.9 mmol) and 2-iodopropane (3.2 g, 18.9 mmol). The reaction was stirred at ambient temperature for 18 h and then partitioned between EtOAc (100 mL) and H2O (100 mL). The layers were separated and the aqueous phase was extracted further with EtOAc (2×100 mL). The combined organic extracts were washed with brine (100 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—75:25 to 50:50, to give the title compound. MS: m/z=233 (M+1).
Reaction SMILES: Cl.[CH3:2][N:3]1[CH2:9][CH2:8][CH2:7][C:6](=O)[CH2:5][CH2:4]1.Cl.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19]N)=[CH:15][CH:14]=1.[OH-].[Na+]>S(=O)(=O)(O)O.O1CCOCC1>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]2[NH:19][C:6]3[CH2:5][CH2:4][N:3]([CH3:2])[CH2:9][CH2:8][C:7]=3[C:15]=2[CH:14]=1
Reactant: CN1CCCC(=O)CC1
Reactant: NNc1ccc(Cl)cc1
Agent: Cl
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: C1COCCO1
Product: CN1CCc2[nH]c3ccc(Cl)cc3c2CC1

Procedure:
The title compound was prepared by following general procedure 1. 1-Methylazepan-4-one hydrochloride (164 mg, 1 mmol) and 4-chlorophenylhydrazine hydrochloride (179 mg, 1 mmol) were heated in a mixture of 7% sulfuric acid in 1,4-dioxane (2-3 mL) overnight under nitrogen. Two liquid layers persisted throughout the reaction. The mixture was poured on to ice and basified with 50% aq NaOH. The resulting precipitate was filtered, washed well with water, and dried in air to give 9-chloro-1,2,3,4,5,6-hexahydro-3-methylazepino[4,5-b]indole as a dark brown solid (183 mg 78% yield).
Reaction SMILES: Br[C:2]1[C:3]([C:26]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:27])=[CH:4][C:5]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:6]([CH:17]=1)[C:7]([O:9]CC1C=CC=CC=1)=[O:8].[CH3:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Li+].Cl>COCCOC.O1CCCC1.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.O>[CH3:34][N:35]1[CH:39]=[C:38]([C:2]2[C:3]([C:26]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[O:27])=[CH:4][C:5]([O:18][CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[C:6]([CH:17]=2)[C:7]([OH:9])=[O:8])[CH:37]=[N:36]1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: O=C(OCc1ccccc1)c1cc(Br)c(C(=O)N2CCOCC2)cc1OCc1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: O=P([O-])([O-])[O-]
Solvent: COCCOC
Solvent: C1CCOC1
Solvent: O
Product: Cn1cc(-c2cc(C(=O)O)c(OCc3ccccc3)cc2C(=O)N2CCOCC2)cn1
Temperature: 130 °C
Reaction time: 18 h

Procedure:
To a solution of phenylmethyl 5-bromo-4-(4-morpholinylcarbonyl)-2-[(phenylmethyl)oxy]benzoate (may be prepared as described in Description 25; 730 mg, 1.430 mmol) in 1,2-dimethoxyethane (6 ml) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (357 mg, 1.72 mmol), tripotassium phosphate (607 mg, 2.86 mmol) and Pd(Ph3P)4 (99 mg, 0.09 mmol) followed by water (0.5 ml). The mixture was heated in a microwave at 130° C. for 90 minutes, cooled and the solvent removed in vacuo. Purification by column chromatography (SiO2; 1:1 ethyl acetate/cyclohexane to 10% 7M NH3 in methanol/dichloromethane) gave the intermediate. To a solution of this intermediate in tetrahydrofuran (4 ml) was added lithium hydroxide (103 mg, 4.29 mmol) and water (0.5 ml). The solution was stirred for 18 hours before neutralising with 2M hydrochloric acid (2.15 ml, 4.29 mmol). The solvent removed in vacuo to give the product as a solid. 603 mg.
Reaction SMILES: [NH2:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:14][C:13]3[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=3[CH2:11][C:10]3[CH:19]=[CH:20][CH:21]=[CH:22][C:9]2=3)=[O:7])=[CH:4][CH:3]=1.[CH3:25][C:26]1[CH:34]=[CH:33][CH:32]=[CH:31][C:27]=1[C:28](Cl)=[O:29]>ClCCl>[CH:19]1[C:10]2[CH2:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[CH2:14][N:8]([C:6]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:28](=[O:29])[C:27]4[CH:31]=[CH:32][CH:33]=[CH:34][C:26]=4[CH3:25])=[CH:24][CH:23]=3)=[O:7])[C:9]=2[CH:22]=[CH:21][CH:20]=1
Reactant: Nc1ccc(C(=O)N2Cc3ccccc3Cc3ccccc32)cc1
Reactant: Cc1ccccc1C(=O)Cl
Solvent: ClCCl
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2Cc3ccccc3Cc3ccccc32)cc1
Yield: 77.1 %

Procedure:
As described for Example 9, 0.942 g (3 mmol) of 5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine is reacted with 0.52 g (3.3 mmol) of 2-methylbenzoyl chloride in 20 ml of dichloromethane. The product is triturated with hexane-ethyl acetate to give 1.0 g of yellow crystals, m.p. 198°-203° C.
Reaction SMILES: [CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6]([O:8][C@H:9]2[C@H:14]([OH:15])[C@@H:13]([OH:16])[C@H:12]([OH:17])[O:11][C@@H:10]2[CH2:18][OH:19])[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22].[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(Cl)Cl>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[C:24]([O:20][C@@H:5]1[C@@H:4]([O:21][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:3]([O:22][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:2]([CH2:1][O:23][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:7][C@@H:6]1[O:8][C@@H:9]1[C@@H:10]([CH2:18][O:19][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:11][CH:12]([O:17][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:13]([O:16][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:14]1[O:15][C:24](=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(OC[C@H]1O[C@H](O[C@H]2[C@H](OC(=O)c3ccccc3)[C@@H](OC(=O)c3ccccc3)C(OC(=O)c3ccccc3)O[C@@H]2COC(=O)c2ccccc2)[C@H](OC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 163.2 %

Procedure:
Maltose (2.0 g, 5.84 mmol) was dissolved in dry pyridine (40 mL) at 0° C. DMAP (cat.) was added. Benzoyl chloride (2.5 equiv., 14.6 mmol, 16.4 g, 13.6 mL) was added dropwise and the solution stirred at room temperature overnight. The solution was poured onto a mixture of ice-water and DCM. The organic layer was washed with NaHCO3(sat.) (×7), brine, H2SO4 (5%) (×2), followed by brine. The solution was dried (Na2SO4) and the solvent evaporated. The product was passed through a short silica plug to remove the remaining benzoyl chloride and the solvent was evaporated to yield 3.5 g (51%) of the white solid product which was reacted on without further purification or characterisation.