Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[C:2]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH:3]([O:10][C:11](=[O:35])[C@H:12]1[CH2:16][C@@H:15]([O:17][Si](C(C)(C)C)(C)C)[CH2:14][N:13]1[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.C([O-])(O)=O.[Na+]>CO.C1COCC1>[O:1]=[C:2]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH:3]([O:10][C:11](=[O:35])[C@H:12]1[CH2:16][C@@H:15]([OH:17])[CH2:14][N:13]1[C:25]([O:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:26])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1C[C@H](C(=O)OC(C(=O)c2ccccc2)c2ccccc2)N(C(=O)OCc2ccccc2)C1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(c1ccccc1)C(OC(=O)[C@H]1C[C@@H](O)CN1C(=O)OCc1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 80.3 %

Procedure:
To a solution of cis-4-(tert-butyldimethylsilyloxy)-N-benzyloxycarbonyl-D-proline 2-oxo-1,2-diphenylethyl ester (21.62 g) in MeOH-THF (2:1, 380 mL) was added 1N HCl (76 mL) at 5° C., and the mixture was stirred at room temperature for 24 hours. To the reaction mixture was added NaHCO3 (6.7 g) at 5° C. The organic solvent was evaporated, and the residue was extracted with EtOAc. The organic layer was washed with water and brine, dried (MgSO4), and evaporated in vacuo. The residue was purified by silica gal column chromatography (hexane-EtOAc, 2:1˜1:3 elution) to give cis4-hydroxy-N-benzyloxycarbonyl-D-proline 2-oxo-1,2-diphenylethyl ester (13.90 g).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[N:4][C:5]([CH2:11][S+:12]([O-:24])[C:13]2[NH:14][C:15]3[CH:16]=[CH:17][C:18]([O:22][CH3:23])=[CH:19][C:20]=3[N:21]=2)=[C:6]([CH3:10])[C:7]=1[O:8][CH3:9].C1(C)C=CC=CC=1.[CH:32]1[CH:37]=[C:36]2[CH:38]=[CH:39][C:40]([OH:53])=[C:41]([C:42]3[C:51]4[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=4)[CH:45]=[CH:44][C:43]=3[OH:52])[C:35]2=[CH:34][CH:33]=1>C1CCCCC1>[CH3:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([CH3:10])[C:5]([CH2:11][S@@:12]([C:13]2[NH:21][C:20]3[CH:19]=[C:18]([O:22][CH3:23])[CH:17]=[CH:16][C:15]=3[N:14]=2)=[O:24])=[N:4][CH:3]=1.[CH:48]1[CH:47]=[C:46]2[CH:45]=[CH:44][C:43]([OH:52])=[C:42]([C:41]3[C:35]4[C:36](=[CH:37][CH:32]=[CH:33][CH:34]=4)[CH:38]=[CH:39][C:40]=3[OH:53])[C:51]2=[CH:50][CH:49]=1
Reactant: COc1ccc2[nH]c([S+]([O-])Cc3ncc(C)c(OC)c3C)nc2c1
Agent: Oc1ccc2ccccc2c1-c1c(O)ccc2ccccc12
Solvent: C1CCCCC1
Solvent: Cc1ccccc1
Product: COc1ccc2nc([S@@](=O)Cc3ncc(C)c(OC)c3C)[nH]c2c1
Temperature: 52.5 °C
Reaction time: 0.62 h
Yield: 85 %

Procedure:
Omeprazole (100 g, 0.2898 mole) was added to a mixture of toluene (1600 ml) and cyclohexane (400 ml) in a round bottom flask kept at 25-30° C. (S)-(−)-BINOL (124.3 g, 0.4346 mole) was added and the content warmed to about 50-55° C. with stirring for 30-45 minutes. The content of the flask was allowed to attain the ambient temperature and then cooled to 0-5° C. with stirring for about an hour. The (S)-omeprazole-(S)-(−)-BINOL complex crystallizes out, filtered and washed with a mixture of cyclohexane/toluene (1:4, v/v) pre-cooled to 0-5° C. The (S)-omeprazole-(S)-(−)-BINOL complex was dried at 35-40° C. under reduced pressure. The e.e. of (S)-omeprazole in the complex was found to be 99.5%. Yield: 85%.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@H:12]([CH:13]=[O:14])[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:17]([Mg]Br)=[CH2:18]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C@H:12]([C@H:13]([OH:14])[CH:17]=[CH2:18])[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=C[Mg]Br
Reactant: CC(C)(C)OC(=O)N1[C@H](C=O)COC1(C)C
Solvent: C1CCOC1
Product: C=C[C@@H](O)[C@@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Temperature: -78 °C
Reaction time: 2 h
Yield: 62 %

Procedure:
To a −78° C. solution of (S)-Garner aldehyde (3, 7.0 g, 30.5 mmol) in dry THF (50 mL) under N2 was slowly added vinylmagnesium bromide (92 mL, 92 mmol, a 1 M solution in THF) via cannula. After the cloudy yellow solution was stirred for 2 h at −78° C., it was warmed to 0° C., and the reaction was quenched with saturated aqueous NH4Cl solution (60 mL). The product was extracted with Et2O (2×60 mL). The combined organic layers were washed with brine (60 mL), dried (Na2SO4), and concentrated. The mixture of erythro and threo diastereomers was separated by column chromatography by gravity (hexane/EtOAc 5:1) to afford 4 (4.8 g, 62%) and its C3-epimer 4a (0.8 g, 10.2%). Compound 4: [α]25D −37.7° (c 1.8, CHCl3); Rf 0.26 (EtOAc/hexane 1:3); 1H NMR (CDCl3) δ 1.48 (s, 3H), 1.50 (s, 9H), 1.58 (s, 3H), 3.91 (m, 2H), 3.98 (m, 1H), 4.25 (m, 1H), 4.39 (m, 1H), 5.24 (m, 1H), 5.38 (m, 1H), 5.85 (m, 1H); 13C NMR (CDCl3) δ 24.2, 26.3, 28.3, 61.8, 64.4, 73.3, 81.4, 94.4, 116.1, 117.8, 137.6, 155.0; ESI-HRMS [M+Na]+ C13H23NO4Na calcd for m/z 280.1525, found 280.1519.
Reaction SMILES: [C:1]([Cl:4])(Cl)=[O:2].C([N:12]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)[CH2:13]1)C1C=CC=CC=1>C1C=CC=CC=1>[Cl:25][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[Cl:24])[O:17][CH:14]1[CH2:15][CH2:16][N:12]([C:1]([Cl:4])=[O:2])[CH2:13]1
Reactant: Clc1ccc(OC2CCN(Cc3ccccc3)C2)cc1Cl
Reactant: O=C(Cl)Cl
Solvent: c1ccccc1
Product: O=C(Cl)N1CCC(Oc2ccc(Cl)c(Cl)c2)C1
Reaction time: 0.5 h
Yield: 4.4 %

Procedure:
To a stirred solution of 275 ml of 2 molar phosgene (0.55 mole) in benzene under nitrogen gas was added dropwise a solution of 0.5 mole of 1-benzyl-3-(3,4-dichlorophenoxy)pyrrolidine in 200 ml of dry benzene. The reaction mixture was stirred an additional 0.5 hr, then was filtered to remove 10 g of the starting pyrrolidine compound as the hydrochloric acid salt. The filtrate was concentrated under reduced pressure to give an oil. The oil was triturated four times in succession with 200 ml each of 30/60 petroleum ether which removed most of the benzyl chloride by-product. The combined petroleum ether when cooled gave 6.5 g of white crystal product which was separated by filtration. The oil residue, after removing excess petroleum ether under vacuum, crystallized. The crystals were separated by filtration and washed with petroleum ether to give 93 g of tan-colored material. Further work-up of the last petroleum ether filtrate gave 17 g additional crude product. Combined yield of crude tan product was 116.5 g (70%), m.p. 79°-84° C. A portion of the crude was recrystallized from 30/60 petroleum ether to give white crystalline product, m.p. 79°-84° C.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:15][NH2:16])=[O:8])[N:6]=1.[NH:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([C:33](O)=[O:34])=[CH:25]1>>[NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:15][NH:16][C:33]([C:26]2[C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[NH:24][CH:25]=2)=[O:34])=[O:8])[N:6]=1
Reactant: O=C(O)c1c[nH]c2ccccc12
Reactant: NC[C@@H]1[C@H]2C[C@H]2CN1C(=O)c1nc(N)sc1-c1cccc(F)c1
Product: Nc1nc(C(=O)N2C[C@@H]3C[C@@H]3[C@H]2CNC(=O)c2c[nH]c3ccccc23)c(-c2cccc(F)c2)s1

Procedure:
prepared by reaction of [2-Amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((1S,2S,5R)-2-aminomethyl-3-aza-bicyclo[3.1.0]hex-3-yl)-methanone with 1H-Indole-3-carboxylic acid. LC-MS (basic): tR=0.76 min; [M+H]+=476.3.
Reaction SMILES: C(N1CCCCC1)=O.S(Cl)(Cl)=O.[Cl:13][C:14]1[C:15]2[N:16]([CH:24]=[C:25]([C:27]([OH:29])=O)[N:26]=2)[CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=1.COC(C1N=C2C([Cl:42])=CC(C(F)(F)F)=CN2C=1)=O>CO.C1(C)C=CC=CC=1>[Cl:13][C:14]1[C:15]2[N:16]([CH:24]=[C:25]([C:27]([Cl:42])=[O:29])[N:26]=2)[CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=1
Reactant: COC(=O)c1cn2cc(C(F)(F)F)cc(Cl)c2n1
Reactant: O=C(O)c1cn2cc(C(F)(F)F)cc(Cl)c2n1
Agent: O=CN1CCCCC1
Solvent: CO
Solvent: Cc1ccccc1
Solvent: O=S(Cl)Cl
Product: O=C(Cl)c1cn2cc(C(F)(F)F)cc(Cl)c2n1
Temperature: 90 °C
Reaction time: 1.25 h

Procedure:
To a 3000 mL three-neck round bottom flask equipped with an overhead stirrer, thermo pocket, addition funnel and nitrogen tube was charged toluene (1000 mL), N-formyl piperidine (3.54 g, 0.031 mol) and thionyl chloride (67 g, 0.559 moles) at 23° C. under nitrogen atmosphere. The resultant reaction mass was heated to 82° C. and to this 8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid (100 g, 0.373 moles) (prepared as in WO 2010/129500) was charged lot wise (5 lots) over a period of 60 min. The walls of the reactor were rinsed with 500 mL toluene. After addition, the resultant reaction mass was stirred at 90° C. for 75 min and the progress of the reaction was monitored by HPLC. For this, 0.5 mL of the reaction mass was diluted with 3 mL of methanol and the formation of acid chloride was analyzed indirectly by detecting its corresponding methyl ester by HPLC). After 2 hours, HPLC analysis indicated about 0.35 a % of unreacted 8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid and about 99.0 a % of 8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid methyl ester. The resultant reaction mass was further heated to 140° C. (oil bath temperature) and distilled at about 109° C. (mass temperature) and 105-107° C. (vapor temperature) at atmospheric pressure over a period of 2.5 hours to remove toluene (about 600 mL) and excess thionyl chloride present in the reaction mass. After distillation, the reaction mass was gradually cooled to 30° C. over a period of 60 min. The concentration of 8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid was about 0.07 a % and the concentration of 8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid methyl ester about 99.2 a % as measured by HPLC at 230 nm.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:13](=[C:14]3[C:19]=1[CH:18]=[CH:17][CH:16]=[CH:15]3)[C:12]1[CH:20]=[CH:21][CH:22]=[CH:23][C:11]=1C1[C:5]2=[CH:6][CH:7]=[CH:8]C=1.C([Li])C[CH2:26][CH3:27].[B:29](OC(C)C)([O:34]C(C)C)[O:30]C(C)C.Cl>CCCCCC.CCOCC>[CH:21]1[C:20]2[C:2]3[C:3]([C:4]4[C:13]([C:12]=2[CH:11]=[CH:23][CH:22]=1)=[CH:8][CH:7]=[CH:6][CH:5]=4)=[CH:27][C:26]([B:29]([OH:34])[OH:30])=[C:14]1[C:19]=3[CH:18]=[CH:17][CH:16]=[CH:15]1
Reactant: Brc1cc2c3ccccc3c3ccccc3c2c2ccccc12
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: [Li]CCCC
Agent: Cl
Solvent: CCOCC
Solvent: CCCCCC
Product: OB(O)c1cc2c3ccccc3c3ccccc3c2c2ccccc12
Temperature: -40 °C
Reaction time: 1 h
Yield: 60 %

Procedure:
Under the atmosphere of argon, 5.87 g of 10-bromobenzo[g]chrysene was placed in a flask, and 100 mL of dehydrated ether was added. After cooling the reaction solution to −40° C., 11 mL of a 1.6M hexane solution of n-butyllithium was added. The resulting solution was heated to 0° C., followed by stirring for 1 hour. The reaction solution was cooled to −60° C., and 10 mL of a dehydrated ether solution of 7.72 g of triisopropyl borate was added dropwise. The reaction solution was stirred for 5 hours while heating to room temperature. 50 mL of a 10% aqueous hydrochloric acid solution was added, followed by stirring for 1 hour. After removing an aqueous phase, and an organic phase was washed with water and saturated saline, and dried with magnesium sulfate. After filtering off magnesium sulfate, the organic phase was concentrated. The resulting solids were washed with hexane, whereby 3.18 g (yield 60%) of benzo[g]chrysene-10-boronic acid as an intended product was obtained.
Reaction SMILES: N1([C:6](N2C=CN=C2)=[O:7])C=CN=C1.[CH:13]1([CH2:16][OH:17])[CH2:15][CH2:14]1.Cl.[F:19][C:20]1[CH:25]=[C:24]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:23]=[CH:22][C:21]=1[N:30]1[C:34]2=[N:35][CH:36]=[N:37][C:38]([S:39][CH:40]3[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]3)=[C:33]2[CH:32]=[N:31]1.C(N(CC)CC)C>CS(C)=O>[CH:13]1([CH2:16][O:17][C:6]([N:43]2[CH2:42][CH2:41][CH:40]([S:39][C:38]3[N:37]=[CH:36][N:35]=[C:34]4[N:30]([C:21]5[CH:22]=[CH:23][C:24]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:25][C:20]=5[F:19])[N:31]=[CH:32][C:33]=34)[CH2:45][CH2:44]2)=[O:7])[CH2:15][CH2:14]1
Reactant: OCC1CC1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CS(=O)(=O)c1ccc(-n2ncc3c(SC4CCNCC4)ncnc32)c(F)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CS(=O)(=O)c1ccc(-n2ncc3c(SC4CCN(C(=O)OCC5CC5)CC4)ncnc32)c(F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 28.6 %

Procedure:
Di-imidazol-1-yl-methanone (0.25 mmol, 41 mg), and cyclopropylmethanol (0.25 mmol, 20 μL) were dissolved in DMSO (2 mL) and stirred for 30 minutes at room temperature. Then, 1-(2-fluoro-4-methanesulfonyl-phenyl)-4-(piperidin-4-ylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride (0.18 mmol, 80 mg) and triethylamine (0.54 mmol, 75 μL) were added. The mixture was heated in a microwave for 5 minutes at 120° C. The progress of the reaction was monitored by thin layer chromatography and LCMS. Purification by HPLC provided Compound A112 as a white solid (26 mg, 29%). 1H NMR (400 MHz, CDCl3) δ (ppm): 8.72 (s, 1H); 8.41 (s, 1H); 7.87 (m, 3H); 4.40 (h, 1H); 4.01 (m, 2H); 3.87 (d, 2H); 3.19 (m, 2H); 3.06 (s, 3H); 2.17 (m, 2H); 1.73 (m, 2H); 1.07 (m, 1H); 0.51 (m, 2H); 0.25 (m, 2H). Exact mass calculated for C22H24FN5O4S2 505.59, found 506.20 (MH+).
Reaction SMILES: C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:8]1[CH:9]=[CH:10][C:11]([N+:15]([O-:17])=[O:16])=[C:12](F)[CH:13]=1.[OH:18][C:19]1[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=1[C:21]([O:23][CH3:24])=[O:22].C(Cl)[Cl:30]>CN(C=O)C>[CH3:24][O:23][C:21](=[O:22])[C:20]1[CH:25]=[CH:26][CH:27]=[CH:28][C:19]=1[O:18][C:10]1[CH:9]=[CH:8][CH:13]=[C:12]([Cl:30])[C:11]=1[N+:15]([O-:17])=[O:16]
Reactant: O=[N+]([O-])c1ccc(Cl)cc1F
Reactant: COC(=O)c1ccccc1O
Reactant: ClCCl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccccc1Oc1cccc(Cl)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 2 h
Yield: 82 %

Procedure:
Cs2CO3 (1.30 g, 4 mmol) was added to a mixture of 5-chloro-2-nitrofluorobenzene (352 mg, 2 mmol) and methyl 2-hydroxybenzoate (0.52 mL, 4 mmol) in DMF (6 mL) and the resulting mixture was stirred at room temperature for 2 h. The mixture was diluted with CH2Cl2, washed with water, dried (Na2SO4), concentrated and flash chromatographed (SiO2, heptane:EtOAc, 10:1-4:1) to give 505 mg (82%) of the title compound (189JO29A). 1H NMR (CDCl3) δ 8.02 (dd, 1 H, J=1.8, 7.8 Hz), 7.96 (d, 1H, J=1.9 Hz), 7.59 (dt, 1H, J=2.0, 7.6 Hz), 7.39 (dd, 1H, J=2.5, 9.0 Hz), 7.24 (dt, 1H, J=1.2, 7.6 Hz), 7.13 (dd, 1H, J=1.2, 8.0 Hz), 6.74 (d, 1H, J=9.0 Hz), 3.77 (s, 3H).
Reaction SMILES: C(O[C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:7]1=O)=O)C.C(OC(C1CC[N:28](CC2C=CC=CC=2)CC1=O)=O)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.CCN(CC)CC>[OH-].[OH-].[Pd+2].CCO>[C:15]([O:14][C:12]([N:9]1[CH2:10][CH2:11][CH:6]2[CH:7]([NH:28][CH2:4]2)[CH2:8]1)=[O:13])([CH3:18])([CH3:17])[CH3:16]
Reactant: CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CC1=O
Reactant: CCOC(=O)C1CCN(Cc2ccccc2)CC1=O
Agent: [Pd+2]
Agent: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCC2CNC2C1
Reaction time: 24 h
Yield: 94.25 %

Procedure:
3-Oxo-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester. A mixture of 1-benzyl-3-oxo-piperidine-4-carboxylic acid ethyl ester (11.31 g, 38 mmol), di-t-butyl dicarbonate (8.78 g, 40.2 mmol), Et3N (5.4 mL, 38.7 mmol) and Pd(OH)2 on carbon (20% on dry basis-Pearlman's catalyst) (1.3 g) were taken into EtOH (110 mL). The mixture was hydrogenated at 60 psi for 24 h in a Parr bottle. The catalyst was removed by filtration and the filtrate was concentrated to dryness to tan solid. Crude residue was shaken well with hexane (100 mL) and filtered. The filtrate was concentrated to yield the title compound (9.70 g, 94.25%). MS (ESI) mass calcd. for C13H21NO5, 271.32; 1H NMR (400 MHz, CDCl3) 4.24 (q, J=7.1, 2H), 4.03 (s br, 2H), 3.49 (t, J=5.6, 2H), 2.32 (m, 3H), 1.47 (s, 9H), 1.31 (t, J=7.1, 3H).
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9](#[N:12])[CH2:10]O>>[CH2:1]([NH:8][CH2:10][C:9]#[N:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#CCO
Reactant: NCc1ccccc1
Product: N#CCNCc1ccccc1
Reaction time: 3 h

Procedure:
Benzyl amine (10.7 grams, 0.1 mole) was added to 8.2 g (0.1 mole) of a 70% aqueous solution of glycolonitrile, HOCH2CN, in a round-bottom flask. The exothermic reaction mixture was stirred for 3 hours with no external heating. The desired product was not recovered.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([S:16]([NH2:19])(=[O:18])=[O:17])[CH:7]=[CH:8][C:9]=1[NH:10][C@@H:11]1[CH2:15][CH2:14][NH:13][CH2:12]1)([O-:3])=[O:2].C(=O)([O-])[O-].[Na+].[Na+].Br[CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33]>CN(C)C=O>[CH3:33][O:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27][N:13]1[CH2:14][CH2:15][C@@H:11]([NH:10][C:9]2[CH:8]=[CH:7][C:6]([S:16]([NH2:19])(=[O:17])=[O:18])=[CH:5][C:4]=2[N+:1]([O-:3])=[O:2])[CH2:12]1
Reactant: NS(=O)(=O)c1ccc(N[C@@H]2CCNC2)c([N+](=O)[O-])c1
Reactant: COCCOCCBr
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCCOCCN1CC[C@@H](Nc2ccc(S(N)(=O)=O)cc2[N+](=O)[O-])C1
Temperature: 60 °C

Procedure:
To a solution of (R)-3-nitro-4-(pyrrolidin-3-ylamino)benzenesulfonamide (440 mg) in N,N-dimethylformamide (10 mL) was added sodium carbonate (132 mg) and 1-bromo-2-(2-methoxyethoxy)ethane (0.155 mL). The reaction mixture was heated at 60° C. for 18 hours and after an aqueous workup, the crude product was purified on silica gel with a 2.5-10% methanol in methylene chloride gradient to provide the title compound.
Reaction SMILES: N[C@H:2]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:3]([N:5]1[CH2:9][C@H:8]2[C@H:10]([NH:13][C:14](=[O:28])[CH:15]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:11][CH2:12][C@H:7]2[CH2:6]1)=[O:4].C=O.[C:35](O)(=O)C.[C:39]([BH3-])#[N:40]>ClCCl>[CH:22]1([CH:15]([CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)[C:14]([NH:13][C@H:10]2[C@H:8]3[C@H:7]([CH2:6][N:5]([C:3](=[O:4])[C@@H:2]([CH2:29][CH:30]([CH3:31])[CH3:32])[N:40]([CH3:39])[CH3:35])[CH2:9]3)[CH2:12][CH2:11]2)=[O:28])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1
Reactant: CC(=O)O
Reactant: [BH3-]C#N
Reactant: CC(C)C[C@@H](N)C(=O)N1C[C@@H]2CC[C@@H](NC(=O)C(C3CCCCC3)C3CCCCC3)[C@@H]2C1
Agent: C=O
Solvent: ClCCl
Product: CC(C)C[C@H](C(=O)N1C[C@@H]2CC[C@@H](NC(=O)C(C3CCCCC3)C3CCCCC3)[C@@H]2C1)N(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To N-((3aS,4R,6aR)-2-((R)-2-amino-4-methylpentanoyl)octahydrocyclopenta[c]pyrrol-4-yl)-2,2-dicyclohexylacetamide (0.133 g, 0.298 mmol) from Step B was added formaldehyde (0.228 mL, 2.98 mmol) in dichloromethane (0.5 mL). Acetic acid (0.5 mL) was added. The reaction was stirred at room temperature for 30 minutes, PS-cyanoborohydride (0.255 g, 0.597 mmol) was then added, and the reaction mixture was stirred at room temperature overnight. The reaction was filtered, and the solvent was removed in vacuo. The crude material was purified on silica gel chromatography on a silica gel cartridge (Analogix®, Burlington, Wis., RS-12) eluting with 1-10% methanol (2 N ammonia)/dichloromethane to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.29 (dd, J=7.1, 15.9, 1H), 4.46-4.35 (m, 1H), 4.09-3.99 (m, 1H), 3.92-3.80 (m, 1H), 3.70 (dd, J=8.6, 12.4, 1H), 3.66-3.58 (m, 2H), 3.45 (dd, J=4.8, 9.1, 0.5H), 2.78-2.64 (m, 1H), 2.63-2.53 (m, 1H), 2.42 (s, 3H), 2.38 (s, 3H), 2.23-2.14 (m, 0.5H), 2.13-1.99 (m, 2H), 1.99-1.82 (m, 5H), 1.82-1.63 (m, 8H), 1.60 (d, J=14.0, 1H), 1.57-1.51 (m, 1H), 1.45 (ddd, J=8.6, 18.8, 29.3, 3H), 1.36-1.05 (m, 9H), 1.01 (d, J=6.6, 3H), 0.91 (dd, J=6.6, 19.9, 3H); MS (ESI+) m/z 474 (M+H)+.
Reaction SMILES: C([CH:19](CCCCCCCCCCCCCCCC)[C:20]([NH2:22])=O)CCCCCCCCCCCCCCCCC.C1C=CC(/C=C/C[O:48][C@@H:49]2[O:54][C@H:53](CO)[C@@H:52](O)[C@H:51](O)[C@H:50]2O)=CC=1.CC(C1C=CC([NH:75][C:76]2[CH:81]=[CH:80][C:79]([C:82]([C:85]3[CH:90]=[CH:89][CH:88]=[CH:87][CH:86]=3)(C)C)=[CH:78][CH:77]=2)=CC=1)(C1C=CC=CC=1)C>>[CH2:20]([NH2:22])[CH2:19][NH2:75].[C:49]([OH:54])(=[O:48])[CH2:50][CH2:51][CH2:52][CH2:53][CH2:86][CH2:87][CH2:88][CH2:89][CH2:90][CH2:85][CH2:82][CH2:79][CH2:80][CH2:81][CH2:76][CH2:77][CH3:78]
Reactant: CCCCCCCCCCCCCCCCCCC(CCCCCCCCCCCCCCCC)C(N)=O
Reactant: CC(C)(c1ccccc1)c1ccc(Nc2ccc(C(C)(C)c3ccccc3)cc2)cc1
Reactant: OC[C@H]1O[C@@H](OC/C=C/c2ccccc2)[C@H](O)[C@@H](O)[C@@H]1O
Product: CCCCCCCCCCCCCCCCCC(=O)O
Product: NCCN
Temperature: 110 °C

Procedure:
In a stainless steel beaker were combined about 3170 grams of stearyl stearamide (KEMA IDE S-180, Witco), about 1553 grams of a rosin ester tackifier resin available commercially as Arakawa KE-100 (glycerol ester of hydrogenated abietic (rosin) acid available from Arakawa Chemical Industries, Ltd. of Osaka Japan) and about 299 grams of Ink Yellow 869 (Milliken Chemical Company). In addition, about 10.0 grams of Uniroyal Naugard 445 anti-oxidant were added. The materials were melted together in a temperature controlled oven at about 140° C. The molten mixture was stirred and further heated in a controlled temperature heating mantle at about 110° C. To this stirred mixture was added about 1266 grams of UNIREZ 2970 (a dimer acid-based tetraamide material manufactured by Union Camp and formed by the reaction of one mole of dimer acid, two moles of ethylene diamine, and two moles of stearic acid) in several portions at a rate so as to avoid freezing the mixture. Offer stirring for about ½ hour, the yellow ink was filtered through a heated Mott apparatus (available from Mott Metallurgical) using #3 Whatman filter paper and a pressure of about 15 psi. The filtered phase change ink was poured into molds and allowed to solidify to form ink sticks.
Reaction SMILES: ClCCCl.[CH3:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N:12]1[CH:16]=[CH:15][N:14]=[C:13]1[S:17][CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27](=[O:32])[CH2:26][CH2:25]2.[O-:33]O.C1(C(C)C)C=CC=CC=1>CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].O>[CH3:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N:12]1[CH:16]=[CH:15][N:14]=[C:13]1[S@:17]([CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27](=[O:32])[CH2:26][CH2:25]2)=[O:33]
Reactant: [O-]O
Reactant: Cc1ccccc1-n1ccnc1SCCCOc1ccc2c(c1)CCC(=O)N2
Agent: [Ti+4]
Agent: CC(C)[O-]
Solvent: O
Solvent: ClCCCl
Solvent: CC(C)c1ccccc1
Product: Cc1ccccc1-n1ccnc1[S@@](=O)CCCOc1ccc2c(c1)CCC(=O)N2
Temperature: -5 °C
Yield: 3.2 %

Procedure:
To 1 l of 1,2-dichloroethane were added 56.8 g of titanium tetraisopropoxide, 168 g of D-(-)-diethyl tartarate, 0.91 ml of water and 80 g of 6-{3-[1-(2-methylphenyl)-2-imidazolylthio]propoxy}-3,4-dihydrocarbostyril. The mixture was stirred and then cooled to -5° C. Thereto was added 124 g of cumene hydroperoxide slowly. After the completion of the addition, the mixture was stirred at 5° C. for 18 hours. The reaction was repeated. The reaction mixtures from the two reactions were combined and purified by a silica gel column chromatography (eluant: dichloromethane/ethyl acetate/methanol=3/1/0→30/10/1), followed by recrystallization from ethanol-ethyl acetate. The mother liquor was concentrated to obtain crystals. This procedure was conducted 14 times. The resulting crystals were purified by a silica gel column chromatography (eluant: dichloromethane/ethyl acetate/methanol=30/10/1), followed by recrystallization from ethanol to obtain 2.7 g of (S)-(+)-6-{3-[1-(2-methylphenyl)-2-imidazolylsulfinyl]propoxy}-3,4-dihydrocarbostyril. White powder.