Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH:5]1[C:11](=[O:12])[CH2:10][C@H:9]2[N:13]([CH3:14])[CH:6]1[CH2:7][CH2:8]2)([O:3][CH3:4])=[O:2].[BH4-].[Na+].[ClH:17]>CO.C(O)C>[ClH:17].[C:1]([CH:5]1[CH:11]([OH:12])[CH2:10][C@H:9]2[N:13]([CH3:14])[CH:6]1[CH2:7][CH2:8]2)([O:3][CH3:4])=[O:2]
Reactant: COC(=O)C1C(=O)C[C@@H]2CCC1N2C
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CO
Product: COC(=O)C1C(O)C[C@@H]2CCC1N2C
Reaction time: 4 h

Procedure:
To a solution of (1RS,2RS)-2-carbomethoxy-3-tropanone (17 g, 85 mmol) in 750 ml methanol cooled to -35° C. was added sodium borohydride (17 g, 450 mmol) and the mixture was stirred for 4 hours. The cooled solution was quenched by slow addition of concentrated hydrochloric acid (40 ml) and the mixture was concentrated in vacuo. Water (400 ml) was added and the pH was adjusted to 3 by addition of concentrated hydrochloric acid. After having washed the water phase three times with diethyl ether pH was adjusted to 11 by addition of concentrated ammonium hydroxide and the water phase was extracted three times with methylene chloride. Concentration in vacuo yields an oil which was dissolved in ethanol and added cocncentrated hydrochloric acid followed by concentration in vacuo. Freeze drying the residue yielded the title compound as an amorphous product.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[CH2:11][C@@H:10]([CH3:26])[C:9]1=[O:27])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+].P(=O)(O)(O)[OH:31]>C1COCC1>[C:17]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:16]=[CH:15][C:14]([CH2:13][C@@H:12]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:11][C@@H:10]([CH3:26])[C:9]([OH:27])=[O:31])=[CH:19][CH:18]=1
Reactant: C[C@@H]1C[C@@H](Cc2ccc(-c3ccccc3)cc2)N(C(=O)OC(C)(C)C)C1=O
Reactant: O=P(O)(O)O
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: C[C@H](C[C@@H](Cc1ccc(-c2ccccc2)cc1)NC(=O)OC(C)(C)C)C(=O)O
Reaction time: 1 h

Procedure:
5 g (3R,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (2-a, R1=BOC) was dissolved in 50 ml of a mixture of THF and a 2 M lithium hydroxide solution (ratio 1:1). After 1 hour at room temperature, phosphoric acid was added to neutralise the excess of lithium hydroxide. The slurry was concentrated under vacuum to remove most of the solvent and extracted with iso-propyl acetate. The organic phase was then washed with water, partially concentrated under vacuum and brought to crystallisation upon addition of heptane. The crystalline solid obtained was collected and dried under vacuum to yield about 3.6 g of [(2R,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid] (3-a, R1=BOC, R2=R3=H). Mpt 146-147° C.; δH (500 MHz; DMSO) 1.07 (3H, d, J 7.0, 1-CH3), 1.34 (9H, s, (CH3)3), 1.38 (1H, m, 3-HA), 1.77 (1H, m, 3-HB), 2.43 (1H, m, 2-H), 2.70 (2H, d, J 7.0, 5-H), 3.69 (1H, m, 4-H), 6.74 (1H, d, J 9.0, NH), 7.27 (2H, d, J 8.0, Ar-ortho-H(Ph)), 7.36 (1H, t, J 7.0, Ar-(Ph)-para-H), 7.46 (2H, t, J 7.5, Ar-(Ph)-meta-H), 7.57 (2H, d, J 8.0, Ar-meta-H(Ph), 7.64 (2H, d, J 7.5, Ar-(Ph)-ortho-H), 12.01 (1H, s, CO2H); δC (500 MHz, DMSO) 18.1 (1-CH3), 28.3 [(CH3)3], 35.9 (2-C), 37.9 (3-C), 40.7 (5-C), 50.0 (4-C), 77.4 [(C(CH3)3], 126.3, 126.5, 127.2, 128.9, 129.8 (Ar—CH), 137.7 (Ar-ipso-C(Ph)), 138.3 (Ar-para-C(Ph)), 140.1 (Ar-(Ph)-ipso-C), 155.2 (NCO), 177.2 (CO2H); m/z (+ESI) 406 ([MNa]+, 6%), 384 ([MH]+, 31), 328 (100), 284 (19). Found: [MH]+, 384.21691. C23H30NO4 requires MH 384.21693.
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([C:7]2[CH:12]=[CH:11][N:10]=[C:9](Cl)[N:8]=2)[S:5][CH:6]=1.C(=O)([O-])[O-].[K+].[K+].[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1>CCO>[Br:1][C:2]1[N:3]=[C:4]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:8]=2)[S:5][CH:6]=1
Reactant: Clc1nccc(-c2nc(Br)cs2)n1
Reactant: C1COCCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: Brc1csc(-c2ccnc(N3CCOCC3)n2)n1
Temperature: 90 °C
Yield: 30.6 %

Procedure:
To a solution of 4-(4-Bromo-thiazol-2-yl)-2-chloro-pyrimidine (25)(0.498 g, 1.8 mmol) in EtOH (8 ml) was added powdered potassium carbonate (0.274 g, 1.98 mmol) and morpholine (0.17 ml, 1.98 mmol). The mixture was heated under the influence of microwave radiation (10 minutes, 90° C., high absorption setting). The reaction mixture was then allowed to cool to room temperature and filtered through a thin pad of silica before being concentrated in vacuo. The crude residue was purified by flash chromatography (SiO2) using Hexanes:EtOAc—(9:1) as eluent to give the title compound (0.18 g, 30.5%) in analytically pure form. m/z (LC-MS, ESP): 327 [M+H]+, R/T=3.92 mins.
Reaction SMILES: C(OC(=O)NC1CC(=O)OC1OCC)C=C.[C:17]([O:21][C:22](=[O:50])[NH:23][CH:24]([CH3:49])[C:25]([N:27]1[CH2:31][CH2:30][CH2:29][CH:28]1[C:32](=[O:48])[NH:33][CH:34]1[CH2:38][C:37](=[O:39])[O:36][CH:35]1[O:40][CH2:41][C:42]1C=CC=CC=1)=[O:26])([CH3:20])([CH3:19])[CH3:18]>>[C:17]([O:21][C:22](=[O:50])[NH:23][CH:24]([CH3:49])[C:25]([N:27]1[CH2:31][CH2:30][CH2:29][CH:28]1[C:32](=[O:48])[NH:33][CH:34]1[CH2:38][C:37](=[O:39])[O:36][CH:35]1[O:40][CH2:41][CH3:42])=[O:26])([CH3:19])([CH3:18])[CH3:20]
Reactant: CC(NC(=O)OC(C)(C)C)C(=O)N1CCCC1C(=O)NC1CC(=O)OC1OCc1ccccc1
Agent: C=CCOC(=O)NC1CC(=O)OC1OCC
Product: CCOC1OC(=O)CC1NC(=O)C1CCCN1C(=O)C(C)NC(=O)OC(C)(C)C
Yield: 73 %

Procedure:
Prepared from (2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester 74 following the method used in the synthesis of 75 to give the title compound as a pale yellow solid (660 mg, 73% yield). 1H-NMR (500 MHz, CD3OD) δ 1.14-1.36 (m, 6H), 1.42 (s, 9H), 1.75-2.29 (m, 4H), 2.48 (dd, 0.5H), 2.58 (dd, 0.5H), 2.72-2.85 (m, 0.5H), 2.99 (dd, 0.5H), 3.43-3.91 (m, 4H), 4.07-4.52 (m, 2.5H), 4.53-4.72 (m, 0.5H), 5.37 (s, 0.5H), 5.57 (d, 0.5H). Analytical HPLC (mixture of 2 diastereomers) 7.92, 8.14 min. LC-MS (ES+) m/e=414.3 (MH+).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[CH2:21][NH:22][CH2:23][CH3:24])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2].C(N(C(C)C)CC)(C)C.Cl[C:36]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:37]>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[CH2:21][N:22]([C:36]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:37])[CH2:23][CH3:24])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2]
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CCNCc1cc(F)ccc1-c1cc(CC(=O)OCC)ccc1OC
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)Cc1ccc(OC)c(-c2ccc(F)cc2CN(CC)C(=O)OCc2ccccc2)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
(2′-Ethylaminomethyl-4′-fluoro-6-methoxy-biphenyl-3-yl)-acetic acid ethyl ester (0,172 g, 0.5 mmol) and diisopropylethylamine (0.18 mL, 1.0 mmol) were combined in CH2Cl2 (2.5 mL) and cooled to 0° C. Benzyl chloroformate (0.1 mL, 0.7 mmol) was added, and the reaction was stirred for 1 hour. The mixture was purified by silica gel chromatography, and then further purified by preparative HPLC to give the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH3:14][Si:15]([CH2:18][CH2:19][O:20][CH2:21]Cl)([CH3:17])[CH3:16]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[CH:9][N:8]([CH2:21][O:20][CH2:19][CH2:18][Si:15]([CH3:17])([CH3:16])[CH3:14])[C:5]2=[N:6][CH:7]=1
Reactant: C[Si](C)(C)CCOCCl
Reactant: Brc1cnc2[nH]cc(I)c2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C[Si](C)(C)CCOCn1cc(I)c2cc(Br)cnc21
Temperature: -40 °C
Reaction time: 1 h
Yield: 73 %

Procedure:
To a 500 ml 3-neck flask, 5-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine (32 g, 99.1 mmol) and DMF (300 ml) were added. The solution was cooled to −40° C. under nitrogen and sodium hydride (2.8 g, 118.9 mmol) was added in 2 batches. The mixture was stirred at −40° C. for 1 hour. Then SEM-Cl (21 ml, 118.9 mmol) in DMF (50 ml) was added drop wise and the resulting mixture was allowed to stir at −40° C. for another 2 hours. The reaction was quenched with saturated NH4Cl (40 ml) and worked up with ethyl acetate, brine, dried with Na2SO4, concentrated to dryness. Silica chromatography of the crude using a gradient of ethyl acetate and hexane afforded 5-bromo-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (32.8 g, 73% yield). NMR (500 MHz, DMSO-d6) δ 0.06 (s, 9H), 0.91 (m, 2H), 3.62 (m, 2H), 5.70 (s, 2H), 8.04 (m, 1H), 8.11 (s, 1H), 8.51 (m, 1H). MS: m/z 455.9 (M+H+).
Reaction SMILES: O.[OH-].[Na+].[O:4]1[CH:8]=[CH:7][CH:6]=[C:5]1[CH:9]=[CH:10][C:11]([NH:13][C@H:14]([C:20]([O-:22])=[O:21])[CH2:15][CH2:16][C:17]([O-:19])=[O:18])=[O:12].Cl>CO>[O:4]1[CH:8]=[CH:7][CH:6]=[C:5]1[CH:9]=[CH:10][C:11]([NH:13][C@H:14]([C:20]([OH:22])=[O:21])[CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[O:12]
Reactant: O=C([O-])CC[C@H](NC(=O)C=Cc1ccco1)C(=O)[O-]
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)CC[C@H](NC(=O)C=Cc1ccco1)C(=O)O
Temperature: 25 °C
Yield: 90 %

Procedure:
To a mixture of 400 ml of water, 80 ml of methanol and 45 g of sodium hydroxide was added 100 g of the dimethyl DL-N-[β-(2-furyl)acryloyl]glutamate, and the resulting mixture was heated at 60° C. to 65° C. for 4 hours to hydrolyze the ester. The reaction mixture was cooled to room temperature and acidified with hydrochloric acid, and thereafter the precipitated crystals were collected by filtration to obtain 80 g (yield 90%) of DL-N-[β-(2-furyl)acryloyl]glutamic acid having a melting point of 166°-170° C.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[C:8]([F:10])[C:5]([CH:6]=O)=[C:4]([F:11])[CH:3]=1.[C:12]([CH:17]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:14][CH2:15][CH3:16])=[O:13]>C1(C)C=CC=CC=1>[CH2:15]([O:14][C:12](=[O:13])[CH:17]=[CH:6][C:5]1[C:8]([F:10])=[CH:9][C:2]([Br:1])=[CH:3][C:4]=1[F:11])[CH3:16]
Reactant: O=Cc1c(F)cc(Br)cc1F
Reactant: CCOC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Product: CCOC(=O)C=Cc1c(F)cc(Br)cc1F
Yield: 91.6 %

Procedure:
A mixture of 4-bromo-2,6-difluoro-benzaldehyde (1 g, 4.5 mmol), (carbethoxymethylene)-triphenyl-phosphorane (2 g, 5.7 mmol) in 30 mL of toluene was heated at reflux for 6 hours, and was evaporated to dryness. The solid was stirred in 200 mL of petroleum ether, and was filtered. The filtrate was evaporated to give the product as oil (1.2 g, yield 91%).
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[F:5][C:6]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([F:16])[C:9]([F:17])=[C:8](F)[C:7]=1[F:19]>CC(C)=O.O>[N:1]([C:8]1[C:7]([F:19])=[C:6]([F:5])[C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([F:16])[C:9]=1[F:17])=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=[N-]
Reactant: COC(=O)c1c(F)c(F)c(F)c(F)c1F
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: COC(=O)c1c(F)c(F)c(N=[N+]=[N-])c(F)c1F
Yield: 86 %

Procedure:
A mixture of NaN3 (0.6 g, 9.22 mmol) and methyl pentafluorobenzoate (1.76 g, 7.78 mmol) in acetone (16 mL) and water (6 mL) was refluxed for 8 hours. The mixture was cooled and then water (20 mL) was added, and the solution was extracted using diethyl ether (3×10 mL). The extracts were dried with Na2SO4 and the mixture was filtered. Solvent was evaporated to give 2 as a white power (1.67 g, yield=86%)
Reaction SMILES: C1C=CC=CC=1.[NH2:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][CH3:16])[CH:11]=[CH:10][C:9]=1[CH3:17].[CH:18](=O)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C([BH3-])#N.[Na+]>O>[CH2:18]([NH:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][CH3:16])[CH:11]=[CH:10][C:9]=1[CH3:17])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=Cc1ccccc1
Reactant: CCOc1ccc(C)c(N)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: c1ccccc1
Solvent: O
Product: CCOc1ccc(C)c(NCc2ccccc2)c1

Procedure:
100 ml of benzene was added to 20.8 g (138 mmol) of 2-amino-4-ethoxytoluene and 17.8 g (168 mmol) of benzaldehyde, and the mixture was heated with refluxing for 5 hours in a reaction vessel equipped with a water separator. After cooling, the reaction solution was concentrated under reduced pressure. 640 ml of methanol was added to the residue, followed by the addition of acetic acid to adjust pH to 5. To this was added 13.1 g (208 mmol) of sodium cyanoborohydride while stirring under cooling with ice, and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated, purified by column chromatography (silica gel, chloroform), and recrystallized (chloroform-n-hexane) to obtain 19.7 g (yield, 59.2%) of colorless prisms of the title compound.
Reaction SMILES: [NH2:1][C:2]1[O:3][CH:4]=[C:5]([CH:7]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:11]([F:21])[CH:10]=2)[CH3:8])[N:6]=1.[CH:22]([O-])([O-])OCC.[BH4-].[Na+]>C(O)C>[F:21][C:11]1[CH:10]=[C:9]([CH:7]([C:5]2[N:6]=[C:2]([NH:1][CH3:22])[O:3][CH:4]=2)[CH3:8])[CH:14]=[CH:13][C:12]=1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: CCOC([O-])[O-]
Reactant: CC(c1ccc(-c2ccccc2)c(F)c1)c1coc(N)n1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CNc1nc(C(C)c2ccc(-c3ccccc3)c(F)c2)co1
Temperature: 25 °C
Reaction time: 2 h
Yield: 40 %

Procedure:
A mixture of 2-amino-4-(1-(2-fluoro-4-biphenylyl) ethyl)oxazole (1.66 g, 5.88 mmol) and ethyl orthoformate (20 ml) was refluxed for 5 hr and the reaction mixture was evaporated under reduced pressure to a residue. To the residue in ethanol (50 ml) was added sodium borohydride (0.27 g, 7.14 mmol) under cooling, then the mixture was stirred at room temperature for 2 hr. After evaporation, the residue was extracted with ethyl acetate and the extracts were washed with water, dried and then evaporated under reduced pressure to a residue, which was chromatographed and recrystallized to afford 4-(1-(2-fluoro-4-biphenylyl)ethyl)-2-methylaminooxazole (0.66 g, 40% yield): mp 133.5°-135.0° C.
Reaction SMILES: [CH2:1]([N:8]1[CH:16]=[N:15][C:14]2[C:9]1=[N:10][C:11]([Cl:18])=[N:12][C:13]=2N)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:19].C(N1C=NC2C1=NC(OCCC)=NC=2N)C1C=CC=CC=1>C(O)CC>[CH2:1]([N:8]1[CH:16]=[N:15][C:14]2[C:9]1=[N:10][C:11]([Cl:18])=[N:12][C:13]=2[Cl:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cl
Reactant: Nc1nc(Cl)nc2c1ncn2Cc1ccccc1
Agent: CCCOc1nc(N)c2ncn(Cc3ccccc3)c2n1
Solvent: CCCO
Product: Clc1nc(Cl)c2ncn(Cc3ccccc3)c2n1

Procedure:
A mixture of 9-benzyl-2-chloro-9H-adenine (130 mg., 0.5 mmole) and 1.25 ml. of 1 N sodium n-propoxide in n-propanol in 13 ml. of n-propanol is refluxed overnight, neutralized with hydrochloric acid and evaporated in vacuo. Trituration of residual material with water provides 118 mg. of crude product which crystallized from aqueous ethanol affords 90 mg. (64%) of analytically pure 9-benzyl-2-n-propoxy-9H-adenine, m.p. 178°-180° C. (dec.). IR(KBr): 3280, 3130, 2970, 1660, 1595, 1405, 1350, 1330, 1275 cm-1. UV:λmaxEtOH 254 nm(ε8,800), 269.5 nm(ε12,800). NMR(CDCl3):δ1.02(3H,t,J=7 Hz), 1.6-2.1(2H,m), 4.25(2H,t,J=7 Hz), 5.20(2H,s), 6.00(2H,br.s), 7.23(5H,m), 7.50(1H,s).
Reaction SMILES: [H-].[Na+].[SH:3][C:4]1[N:5]([CH3:9])[CH:6]=[CH:7][N:8]=1.Br[CH2:11][CH2:12][CH2:13][O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][O:16]1>CN(C=O)C.O>[CH3:9][N:5]1[CH:6]=[CH:7][N:8]=[C:4]1[S:3][CH2:11][CH2:12][CH2:13][O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][O:16]1
Reactant: BrCCCOC1CCCCO1
Reactant: Cn1ccnc1S
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cn1ccnc1SCCCOC1CCCCO1
Temperature: 100 °C
Reaction time: 0.5 h
Yield: 51.3 %

Procedure:
Sodium hydride (0.95 g of a 50% suspension in mineral oil, 20 mmol) was added to a solution of 2-mercapto-1-methylimidazole (2.26 g, 19 mmol) in DMF (100 ml) and the mixture stirred for 30 minutes. 2-(3-Bromopropoxy)tetrahydropyran (5.0 g, 22.5 mmol), (J. Chem. Soc. 1963, 3440), was added and the mixture heated at 100° C. for 3 hours and then stirred at ambient temperature for 18 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed with water, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol mixtures (100/0 increasing to 97/3) to give 1-methyl-2-(3-(2-tetrahydropyranyloxy)propylthio)imidazole (2.5 g, 55%). 1H NMR Spectrum: (DMSOd6) 1.38-1.72(m, 6H); 1.80(m, 2H); 3.0(t, 2H); 3.36-343(m, 2H); 3.58(s, 3H); 3.62-3.78(m, 2H); 4.50(s, 1H); 6.90(s, 1H); 7.21(s, 1H)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1.Cl[CH2:24][C:25]1[CH:30]=[CH:29][N:28]=[C:27]([C:31]2[CH:36]=[C:35]([O:37][CH3:38])[C:34]([O:39][CH3:40])=[C:33]([O:41][CH3:42])[CH:32]=2)[CH:26]=1>>[C:19]([O:18][C:16]([N:13]1[CH2:14][CH2:15][CH:10]([N:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[CH2:24][C:25]2[CH:30]=[CH:29][N:28]=[C:27]([C:31]3[CH:36]=[C:35]([O:37][CH3:38])[C:34]([O:39][CH3:40])=[C:33]([O:41][CH3:42])[CH:32]=3)[CH:26]=2)[CH2:11][CH2:12]1)=[O:17])([CH3:22])([CH3:21])[CH3:20]
Reactant: COc1cc(-c2cc(CCl)ccn2)cc(OC)c1OC
Reactant: COc1ccc(NC2CCN(C(=O)OC(C)(C)C)CC2)cc1
Product: COc1ccc(N(Cc2ccnc(-c3cc(OC)c(OC)c(OC)c3)c2)C2CCN(C(=O)OC(C)(C)C)CC2)cc1

Procedure:
4-(p-Anisidino)-1-(tert-butoxycarbonyl)piperidine (2.21 g) and 4-chloromethyl-2-(3,4,5-trimethoxyphenyl)pyridine (2.12 g) were condensed in the same manner as described in Example 9 to give the title compound.
Reaction SMILES: CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH:23]1([C:29]2[C:30]3[CH:31]=[CH:32][C:33]([C:50]([O:52][CH3:53])=[O:51])=[CH:34][C:35]=3[N:36]3[CH2:42][CH:41]([C:43](O)=[O:44])[CH2:40][C:39]4[CH:46]=[CH:47][CH:48]=[CH:49][C:38]=4[C:37]=23)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.[NH:54]1[CH2:59][CH2:58][O:57][CH2:56][CH2:55]1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH:23]1([C:29]2[C:30]3[CH:31]=[CH:32][C:33]([C:50]([O:52][CH3:53])=[O:51])=[CH:34][C:35]=3[N:36]3[CH2:42][CH:41]([C:43]([N:54]4[CH2:59][CH2:58][O:57][CH2:56][CH2:55]4)=[O:44])[CH2:40][C:39]4[CH:46]=[CH:47][CH:48]=[CH:49][C:38]=4[C:37]=23)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: C1COCCN1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CC(C(=O)O)Cc1ccccc1-3
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CC(C(=O)N1CCOCC1)Cc1ccccc1-3
Temperature: 22 °C
Reaction time: 18 h
Yield: 85.8 %

Procedure:
TBTU (69 mg, 0.22 mmol) was added to a stirred solution of racemic 14b (60 mg, 0.0.144 mmol), morpholine (19 μL, 0.22 mmol), and N,N-diisopropylethylamine (300 μL, 1.7 mmol) in DMF (3 mL). The mixture was shaken at 22° C. for 18 hr. The resulting solution was injected on a Shimadzu preparative liquid chromatograph. The product containing fraction was concentrated on a Speed Vac® to leave methyl 13-cyclohexyl-6,7-dihydro-6-(morpholinylcarbonyl)-5H-indolo[2,1-a][2]benzazepine-10-carboxylate as a colorless solid (60 mg, 86%). ESI-MS m/z 487 (MH+).
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:6]2[N:5]=[CH:4][C:3]=1[C:16]([O:18][CH3:19])=[O:17].[CH3:20][C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=1>>[CH2:14]([O:13][C:11]([C:10]1[CH:9]=[N:8][N:7]2[C:2]([NH:25][C:24]3[CH:26]=[CH:27][C:21]([CH3:20])=[CH:22][CH:23]=3)=[C:3]([C:16]([O:18][CH3:19])=[O:17])[CH:4]=[N:5][C:6]=12)=[O:12])[CH3:15]
Reactant: Cc1ccc(N)cc1
Reactant: CCOC(=O)c1cnn2c(Cl)c(C(=O)OC)cnc12
Product: CCOC(=O)c1cnn2c(Nc3ccc(C)cc3)c(C(=O)OC)cnc12
Yield: 35.7 %

Procedure:
In the same manner as in Example 1, step 4 and using methyl 7-chloro-3-ethoxycarbonylpyrazolo[1,5-a]pyrimidine-6-carboxylate (0.400 g, 1.51 mmol) obtained in Example 21, step 2 and 4-methylaniline (0.242 g, 2.26 mmol), the title compound (0.191 g, 35%) was obtained.
Reaction SMILES: [CH3:1][C@:2]([OH:7])([CH2:5]Cl)[CH2:3][OH:4].[H-].[Na+].[CH3:10][O:11][C:12]1[C:19]([CH3:20])=[C:18]([CH3:21])[C:17]([O:22][CH3:23])=[C:16]([CH3:24])[C:13]=1[CH2:14][Li].COC1C(C)=C(C)C(OC)=C(C)C=1C>O1CCCC1.O>[CH3:1][C@:2]([OH:7])([CH2:5][CH2:21][C:18]1[C:19]([CH3:20])=[C:12]([O:11][CH3:10])[C:13]([CH3:14])=[C:16]([CH3:24])[C:17]=1[O:22][CH3:23])[CH2:3][OH:4]
Reactant: C[C@@](O)(CO)CCl
Reactant: [Li]Cc1c(C)c(OC)c(C)c(C)c1OC
Agent: COc1c(C)c(C)c(OC)c(C)c1C
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COc1c(C)c(C)c(OC)c(CC[C@](C)(O)CO)c1C
Reaction time: 1 h
Yield: 101.8 %

Procedure:
A solution of 9.78 g (80 mmol) of (2R)-2-methyl-3-chloropropane-1,2-diol in 100 ml of tetrahydrofuran was reacted with 4.3 g (180 mmol) of sodium hydride at room temperature by the portionwise addition while stirring for 1 hour. To the suspension obtained there was added dropwise, while stirring at room temperature, a solution of 88 mmol of 2,5-dimethoxy-3,4,6-trimethylbenzyl lithium (obtained by reacting 17.2 g (88 mmol) of 2,5-dimethoxy-1,3,4,6-tetramethylbenzene in 20 ml of n-pentane with 88 mmol of tert.butyl lithium at room temperature) and the mixture was subsequently stirred at room temperature for an additional 16 hours. The mixture was then treated with 50 ml of water while stirring, the volatile constituents were removed by distillation in a vacuum (~15 mbar) and the separated material was removed by filtration and washed with water. The filter residue was recrystallized from ether/hexane and there were obtained 23 g of (2S)-2-methyl-4-(2,5 -dimethoxy-3,4,6-trimethylphenyl)-1,2-butanediol in the form of white crystals with a melting point of 83°-85° C. and [α]D20 =+2.86° (c=1.5% in CHCl3).
Reaction SMILES: [C:1]1([C@H:7]([O:9][C:10](=[O:24])[NH:11][C:12]2[N:13]=[CH:14][O:15][C:16]=2[C:17]2[CH:22]=[CH:21][C:20](Br)=[CH:19][CH:18]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:25]([O:27][C:28]([C:30]1([C:33]2[CH:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=2)[CH2:32][CH2:31]1)=[O:29])[CH3:26]>Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:25]([O:27][C:28]([C:30]1([C:33]2[CH:38]=[CH:37][C:36]([C:20]3[CH:21]=[CH:22][C:17]([C:16]4[O:15][CH:14]=[N:13][C:12]=4[NH:11][C:10]([O:9][C@@H:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH3:8])=[O:24])=[CH:18][CH:19]=3)=[CH:35][CH:34]=2)[CH2:31][CH2:32]1)=[O:29])[CH3:26]
Reactant: CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Reactant: C[C@@H](OC(=O)Nc1ncoc1-c1ccc(Br)cc1)c1ccccc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4ocnc4NC(=O)O[C@H](C)c4ccccc4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 1, Step 2, using the following starting materials: [5-(4-bromo-phenyl)-oxazol-4-yl]-carbamic acid (R)-1-phenyl-ethyl ester and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester. Additionally, (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) was used as the catalyst.