Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS(O[CH2:6][CH2:7][C:8]1([CH3:19])[O:12][C:11]2=[N:13][C:14]([N+:16]([O-:18])=[O:17])=[CH:15][N:10]2[CH2:9]1)(=O)=O.Cl.[C:21]([N:25]1[CH2:30][CH2:29][NH:28][CH2:27][C:26]1=[O:31])([CH3:24])([CH3:23])[CH3:22].C(N(CC)CC)C.[I-].[K+]>O.CN(C=O)C>[C:21]([N:25]1[CH2:30][CH2:29][N:28]([CH2:6][CH2:7][C:8]2([CH3:19])[O:12][C:11]3=[N:13][C:14]([N+:16]([O-:18])=[O:17])=[CH:15][N:10]3[CH2:9]2)[CH2:27][C:26]1=[O:31])([CH3:24])([CH3:22])[CH3:23]
Reactant: CC(C)(C)N1CCNCC1=O
Reactant: CC1(CCOS(C)(=O)=O)Cn2cc([N+](=O)[O-])nc2O1
Agent: Cl
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC1(CCN2CCN(C(C)(C)C)C(=O)C2)Cn2cc([N+](=O)[O-])nc2O1
Temperature: 70 °C
Reaction time: 4 h
Yield: 7.7 %

Procedure:
A mixture of 2-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-yl)ethyl methanesulfonate prepared in Example 42 (290 mg, 1 mmol), 1-tert-butylpiperazin-2-one hydrochloride (200 mg, 1.28 mmol), triethylamine (242 mg, 2.39 mmol), potassium iodide (250 mg, 1.5 mmol) and DMF (3 ml) was stirred at 70° C. for 4 hours. The reaction mixture was allowed to return to room temperature. To the solution, water was added, and the resulting solution was extracted with ethyl acetate twice. The organic phases were combined, washed with water twice and a saturated saline solution, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=20/1) to afford 1-tert-butyl-4-[2-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-yl)ethyl]piperazin-2-one (27 mg, yield 8%) as a white powder.
Reaction SMILES: [N:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH:6]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]3[C:24](=[O:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]3=[O:26])[C:5]=2[N:4]=[CH:3][CH:2]=1.[C:27]([O:31][C:32]([N:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[N:36]=[C:35]1[CH2:43]Cl)=[O:33])([CH3:30])([CH3:29])[CH3:28].[I-].[K+].C(N(C(C)C)CC)(C)C.C(=O)(O)[O-].[Na+]>CC#N>[C:27]([O:31][C:32]([N:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[N:36]=[C:35]1[CH2:43][N:11]([CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:17](=[O:26])[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:24]1=[O:25])[CH:6]1[CH2:7][CH2:8][CH2:9][C:10]2[N:1]=[CH:2][CH:3]=[N:4][C:5]1=2)=[O:33])([CH3:30])([CH3:29])[CH3:28]
Reactant: O=C1c2ccccc2C(=O)N1CCCCNC1CCCc2nccnc21
Reactant: CC(C)(C)OC(=O)n1c(CCl)nc2ccccc21
Agent: O=C([O-])O
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)n1c(CN(CCCCN2C(=O)c3ccccc3C2=O)C2CCCc3nccnc32)nc2ccccc21
Temperature: 60 °C
Reaction time: 17 h
Yield: 85.5 %

Procedure:
To a solution of 2-[4-(5,6,7,8-tetrahydro-quinoxalin-5-ylamino)-butyl]-isoindole-1,3-dione (298 mg, 0.850 mmol) in CH3CN (12 mL) was added 2-chloromethyl-benzoimidazole-1-carboxylic acid tert-butyl ester (295 mg, 1.11 mmol), potassium iodide (14 mg), and diisopropylethylamine (0.296 ml, 1.70 mmol). The reaction mixture was stirred at 60° C. for 17 hours. Saturated sodium bicarbonate (15 mL) was added and the mixture was extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. Purification of the crude material by column chromatography on silica gel (1:10 EtOAc:hexanes then EtOAc then 1:10 MeOH:EtOAc) provided the product as a clear oil (422 mg, 85%): 1H NMR (CDCl3): δ 1.34-1.43 (m, 2H), 1.48-1.60 (m, 2H), 1.68 (s, 9H), 1.71-1.81 (m, 1H), 1.88-1.97 (m, 1H), 2.00-2.21 (m, 2H), 2.60-2.69 (m, 1H), 2.76-2.93 (m, 3H), 3.55 (t, 2H, J=6.9 Hz), 4.29 (dd, 1H, J=9.6, 5.4 Hz), 4.46 (d, 1H, J=15.3 Hz), 4.61 (d, 1H, J=15.3 Hz), 7.19-7.24 (m, 2H), 7.63-7.69 (m, 3H), 7.74-7.81 (m, 3H), 8.18 (d, 1H, J=2.1 Hz), 8.27 (d, 1H, J=2.1 Hz).
Reaction SMILES: [C:1]1([C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[NH2:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14](Cl)Cl.[OH-].[Na+]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C(Cl)(Cl)Cl>[C:1]1([C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[N+:9]#[C-:14])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: ClCCl
Reactant: Nc1ccccc1-c1ccccc1
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: [C-]#[N+]c1ccccc1-c1ccccc1

Procedure:
A reaction flask was charged with 17 g (0.1 mole) of 2-phenylaniline, 20 ml of methylene chloride, 15 ml of chloroform, 30 ml of 50% aqueous sodium hydroxide, and 200 mg of benzyltriethylammonium chloride. The procedure of Example 1 was followed, yielding 6 g of a thick oil, whose structure was confirmed by mass spectroscopy as that indicated by the above title.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:12])[CH2:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1)[CH3:2].[H-].[Na+].C1OCCOCCOCCOCCOCC[O:17][CH2:16]1.C(OC=O)C.[Cl-].[NH4+]>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:12])[C:5]([C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1)=[CH:16][OH:17])[CH3:2]
Reactant: CCOC(=O)Cc1cccnc1
Reactant: C1COCCOCCOCCOCCOCCO1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CCOC=O
Solvent: Cc1ccccc1
Product: CCOC(=O)C(=CO)c1cccnc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
1.65 g (10.0 mmol) 3-pyridylacetic acid ethyl ester are initially introduced into 20 ml anhydrous toluene under argon. 410 mg (10.3 mmol) sodium hydride suspension (60% strength in paraffin oil) and 130 mg (0.50 mmol) 18-crown-6 are added in portions to the solution and the mixture is stirred at RT for 30 min and then at 85° C. (bath temperature) for 30 min. After this time, the mixture is cooled and 1.48 g (20.0 mol) formic acid ethyl ester are added dropwise at approx. 20° C. The mixture is stirred first at RT for 60 min and then at 90° C. (bath temperature) for 60 min. After cooling, the reaction solution is introduced on to approx. 50 ml saturated ammonium chloride solution and extracted with ethyl acetate (five times with 40 ml each time). The combined organic phases are washed with 50 ml saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The solid obtained is washed with pentane and dried in vacuo.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:30]=[O:31])[C:5]2[C:6]([CH:29]=1)=[N:7][N:8]([CH2:10][C:11]([NH:15][C:16](=[O:28])[C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=1)([C:13]#[N:14])[CH3:12])[N:9]=2.CC(=CC)C.Cl[O-].[Na+].P([O-])(O)(O)=[O:41].[Na+]>C1COCC1.O.C(O)(C)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:30]([OH:41])=[O:31])[C:5]2[C:6]([CH:29]=1)=[N:7][N:8]([CH2:10][C:11]([C:13]#[N:14])([NH:15][C:16]([C:17]1[CH:18]=[CH:19][C:20]([O:23][C:24]([F:26])([F:25])[F:27])=[CH:21][CH:22]=1)=[O:28])[CH3:12])[N:9]=2
Reactant: O=P([O-])(O)O
Reactant: CC(C#N)(Cn1nc2cc(Cl)cc(C=O)c2n1)NC(=O)c1ccc(OC(F)(F)F)cc1
Agent: CC=C(C)C
Agent: [Na+]
Agent: [O-]Cl
Solvent: O
Solvent: CC(C)(C)O
Solvent: C1CCOC1
Product: CC(C#N)(Cn1nc2cc(Cl)cc(C(=O)O)c2n1)NC(=O)c1ccc(OC(F)(F)F)cc1
Reaction time: 4 h
Yield: 86.9 %

Procedure:
To a solution of N-[2-(6-Chloro-4-formyl-2H-benzotriazol-2-yl)-1-cyano-1-methylethyl]-4-trifluoromethoxybenzamide (1.5 g) in a mixture of THF (25 mL), t-butanol (10 mL) and 2-methyl-2-butene was added dropwise the solution of sodium hypochlorite (0.9 g) and sodium dihydrogen phosphate (1.15 g) in water (20 mL). After 4 hour at room temperature, the mixture was concentrated under reduced pressure, diluted with water (50 mL) and acidified to pH 2 with normal HCl. The white solid was filtered and washed with water and dried under vacuum to give the title compound (1.35 g, 87%). MS (ES): M/Z [M+H]=468. 1H NMR: (400 MHz, DMSO-d6): 1.72 (s, 3H), 5.48-5.64 (m, 2H), 7.43 (d, J=8.2 Hz, 2H), 7.83 (d, J=2.0 Hz, 1H), 7.99 (d, J=8.8 Hz, 2H), 8.23 (d, J=1.8 Hz, 0H) and 9.41 (br. s, 1H). 19F NMR (376 MHz, DMSO-d6): −57.1 (s, 3F).
Reaction SMILES: Cl.C([O:9][CH2:10][C@@H:11]1[O:16][CH2:15][C@@:14]([NH:25][C:26]([NH:28]C(=O)OCC2C3C=CC=CC=3C3C2=CC=CC=3)=[S:27])([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[F:24])[C@H:13]([CH2:46]O)[CH2:12]1)C1C=CC=CC=1>CO>[NH2:28][C:26]1[S:27][CH2:46][C@@H:13]2[CH2:12][C@H:11]([CH2:10][OH:9])[O:16][CH2:15][C@:14]2([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[F:24])[N:25]=1
Reactant: O=C(NC(=S)N[C@@]1(c2ccc(F)cc2F)CO[C@@H](COCc2ccccc2)C[C@H]1CO)OCC1c2ccccc2-c2ccccc21
Agent: Cl
Solvent: CO
Product: NC1=N[C@@]2(c3ccc(F)cc3F)CO[C@@H](CO)C[C@H]2CS1
Temperature: 70 °C

Procedure:
Concentrated hydrochloric acid (12 M, 17.6 mL) was added to a methanol solution of 9H-fluoren-9-ylmethyl {[(3S,4R,6R)-6-[(benzyloxy)methyl]-3-(2,4-difluorophenyl)-4-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]carbamothioyl}carbamate (C23) (995 mg, 1.54 mmol), and the reaction mixture was heated to 70° C. for 2 hours. At this point, LCMS analysis indicated that the starting material had been consumed. The methanol was allowed to distill off, and the aqueous residue was heated to 120° C. for 3 hours. The reaction mixture was partitioned between water and ethyl acetate, and the aqueous layer was extracted with ethyl acetate. These organic layers were shown by chromatographic separation, followed by 1H NMR and LCMS analysis, to contain cyclized material still retaining the fluorenylmethoxycarbonyl protecting group. The aqueous layer was basified with saturated aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. These extracts were combined, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was triturated with dichloromethane to afford the product as a white solid. The filtrate from the trituration was concentrated in vacuo and triturated with dichloromethane to afford additional product, also as a white solid. Yield: 235 mg, 0.748 mmol, 49%. LCMS m/z 315.3 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.41-1.47 (m, 1H), 1.84-1.96 (m, 1H), 2.61-2.68 (m, 1H), 2.92-3.01 (m, 2H), 3.65 (dd, half of ABX pattern, J=11.7, 6.7 Hz, 1H), 3.70 (dd, half of ABX pattern, J=11.7, 3.2 Hz, 1H), 3.73-3.81 (m, 1H), 3.85 (d, J=11.3 Hz, 1H), 4.11 (dd, J=11.2, 2.2 Hz, 1H), 6.82 (ddd, J=12.4, 8.5, 2.6 Hz, 1H), 6.86-6.92 (m, 1H), 7.34 (ddd, J=9.1, 9.0, 6.7 Hz, 1H).
Reaction SMILES: [Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:9]([OH:12])[CH2:10][OH:11].C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1>[Si:1]([O:11][CH2:10][CH2:9][OH:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: OCCO
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCCO
Temperature: 25 °C
Reaction time: 3 h

Procedure:
tert-Butyldimethylsilylchloride (100 g, 0.66M) in dry dichloromethane (70 ml) was added, drop-wise, to a stirred mixture of distilled ethylene glycol (205.6 g, 3.31M), dry dichloromethane (200 ml), triethylamine (120 ml, 0.86M) and 4-dimethylaminopyridine (8 g, 0.066M) at 0° C. under a nitrogen atmosphere. After the addition the mixture was allowed to warm to ambient temperature and was stirred for a further 3 hours. The mixture was then filtered and the filtrate washed with dilute sodium bicarbonate solution, brine, dried over magnesium sulphate, filtered and then evaporated in vacuo to give a pale yellow oil.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.O[C:14]1[CH:15]=[C:16]([CH2:20][C:21]#[N:22])[CH:17]=[CH:18][CH:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:42][CH2:43][CH2:44][NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49]>O1CCCC1.C(OCC)(=O)C>[C:21]([CH2:20][C:16]1[CH:17]=[CH:18][CH:19]=[CH:14][C:15]=1[O:42][CH2:43][CH2:44][NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])#[N:22]
Reactant: CC(C)(C)OC(=O)NCCO
Reactant: N#CCc1cccc(O)c1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)NCCOc1ccccc1CC#N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Diethyl azodicarboxylate (6.2 ml, 39.4 mmol) was added dropwise to an ice-cooled solution of 3-hydroxyphenyl acetonitrile (preparation 126) (4.2 g, 31.5 mmol), triphenylphosphine (10.34 g, 39.4 mmol) and tert-butyl 2-hydroxyethylcarbamate (5.4 ml, 34.9 mmol) in tetrahydrofuran (70 ml), and once addition was complete, the reaction was stirred at room temperature overnight. The reaction was diluted with ethyl acetate (400 ml), washed with 1N NaOH solution, water, brine, then dried over MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using ethyl acetate:pentane (30:70) as eluant to give the desired product as a yellow/green oil, that crystallised on standing, (5.88 g, 68%).
Reaction SMILES: [C:1]1(=[O:8])[CH2:6][CH2:5][CH2:4][C:3](=[O:7])[CH2:2]1.C([O-])([O-])=O.[Na+].[Na+].[O:15](S(C(F)(F)F)(=O)=O)[S:16]([C:19]([F:22])([F:21])[F:20])(=O)=[O:17]>C(Cl)Cl>[F:20][C:19]([F:22])([F:21])[S:16]([O:7][C:3]1[CH2:4][CH2:5][CH2:6][C:1](=[O:8])[CH:2]=1)(=[O:17])=[O:15]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: O=C1CCCC(=O)C1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: O=C1C=C(OS(=O)(=O)C(F)(F)F)CCC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 67 %

Procedure:
To a solution of cyclohexane-1,3-dione (1 equiv) in DCM (0.4 M) was added Na2CO3 (1.0 equiv.) and cooled to 0° C. Added Tf2O (1.0 equiv.) in DCM (5 M) dropwise over 1 hr at room temperature under a nitrogen atmosphere. Upon addition, the reaction was stirred for 2 hr (dark red solution). The solution was filtered and to the filtrate was added saturated NaHCO3 (carefully), then extracted the organics, dried with brine, then Na2SO4, and concentrated. The crude was used for the next step without further purification. 3-oxocyclohex-1-enyl trifluoromethanesulfonate was obtained in 67% yield. The triflate decomposes upon storage and should be used immediately for the next reaction. LC/MS=244.9/286.0 (M+H and M+CH3CN); Rt=0.88 min.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:8][CH:9]([F:11])[F:10].[CH3:12][C:13]1[N:14]=[CH:15][N:16]([C:18]2[C:19]([OH:45])=[N:20][C:21](/[CH:24]=[CH:25]/[C:26]3[N:44]=[C:29]4[C@H:30]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=5[C:40]([F:43])([F:42])[F:41])[CH2:31][CH2:32][CH2:33][N:28]4[N:27]=3)=[CH:22][CH:23]=2)[CH:17]=1.CN(C=O)C>C(OCC)(=O)C.O>[CH3:12][C:13]1[N:14]=[CH:15][N:16]([C:18]2[CH:23]=[CH:22][C:21](/[CH:24]=[CH:25]/[C:26]3[N:44]=[C:29]4[CH:30]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=5[C:40]([F:42])([F:43])[F:41])[CH2:31][CH2:32][CH2:33][N:28]4[N:27]=3)=[N:20][C:19]=2[O:45][CH2:8][CH:9]([F:11])[F:10])[CH:17]=1
Reactant: FC(F)CBr
Reactant: Cc1cn(-c2ccc(/C=C/c3nc4n(n3)CCC[C@H]4c3ccccc3C(F)(F)F)nc2O)cn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cn(-c2ccc(/C=C/c3nc4n(n3)CCCC4c3ccccc3C(F)(F)F)nc2OCC(F)F)cn1
Temperature: 25 °C
Reaction time: 48 h
Yield: 70.3 %

Procedure:
Cesium carbonate (83.7 mg) and 2-bromo-1,1-difluoroethane (34.1 mg) were added to a mixture of 3-(4-methyl-1H-imidazol-1-yl)-6-{(E)-2-[8-(2-trifluoromethylphenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl]vinyl}pyridin-2-ol synthesized in Example 344 (100 mg) and DMF (1.2 mL), and the reaction solution was stirred at room temperature for 48 hours. Water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (carrier: Chromatorex NH; elution solvent: heptane:ethyl acetate=4:1→ethyl acetate) to obtain a racemate of the title compound (80 mg). The resulting racemate (80 mg) was separated by CHIRALPAK™ IB manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm, mobile phase: hexane:ethanol=4:6, flow rate: 11 mL/min) to obtain the title optically active compound with a retention time of 14 minutes and positive optical rotation (33 mg) and the title optically active compound with a retention time of 25 minutes and negative optical rotation (35 mg).
Reaction SMILES: CO[CH:3](OC)[CH2:4][NH:5][C:6](=[O:18])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=1.Cl>C(O)(=O)C>[CH3:15][O:14][C:11]1[C:10]([O:16][CH3:17])=[CH:9][C:8]2[CH2:7][C:6](=[O:18])[NH:5][CH:4]=[CH:3][C:13]=2[CH:12]=1
Reactant: COc1ccc(CC(=O)NCC(OC)OC)cc1OC
Agent: Cl
Solvent: CC(=O)O
Product: COc1cc2c(cc1OC)CC(=O)NC=C2
Temperature: 0 °C
Reaction time: 8 h

Procedure:
The acetamide (40 g.) was mixed with 200 ml. of concentrated hydrochloric acid and 200 ml. of glacial acetic acid and allowed to stand at room temperature overnight. The reaction mixture was poured into ice/water and the resulting solid was washed with water/methanol to give 2,3-dihydro-7,8-dimethoxy-2-oxo-1H-3-benzazepine, m.p. 239°-241° C.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]([C:9]1[CH:14]=[C:13]([C:15]([NH:17][CH2:18][CH2:19][CH2:20][O:21][CH3:22])=[O:16])[CH:12]=[CH:11][N:10]=1)=[O:8].C1C=C(Cl)C=C(C(OO)=[O:31])C=1>>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH+:6]([O-:31])[C:7]([C:9]1[CH:14]=[C:13]([C:15]([NH:17][CH2:18][CH2:19][CH2:20][O:21][CH3:22])=[O:16])[CH:12]=[CH:11][N:10]=1)=[O:8]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COCCCNC(=O)c1ccnc(C(=O)NCCCOC)c1
Product: COCCCNC(=O)c1ccnc(C(=O)[NH+]([O-])CCCOC)c1

Procedure:
From 1 g of N,N'-di-(3-methoxypropyl)pyridine-2,4-dicarboxamide and 1.2 g of MCPBA.
Reaction SMILES: [Cl:1][C:2]([CH2:4]Cl)=[CH2:3].[CH2:6]([OH:13])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C1(C)C=CC=CC=1>[Zn].O>[Cl:1][C:2](=[CH2:3])[CH2:4][CH:6]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[OH:13]
Reactant: C=C(Cl)CCl
Reactant: CCCCCCCO
Agent: [Zn]
Solvent: Cc1ccccc1
Solvent: O
Product: C=C(Cl)CC(O)CCCCCC
Yield: 94.1 %

Procedure:
58.30 Grams of 2,3-dichloro-1-propene were added dropwise to a mixture of 30.00 g of heptanol, 90 g of toluene, 120 g of water and 34.35 g of zinc powder at 45° C., and then, the resultant mixture was allowed to react at the same temperature for 10 hours. After the reaction finished, zinc-derived insolubles were filtered off, and the resultant filtrate was subjected to separation. The organic phase was washed with a 7% sodium carbonate aqueous solution and then dried over sodium sulfate. The desiccant was filtered off, and then the toluene was distilled off under reduced pressure to give 47.14 g of 2-chloroallyl-n-hexyl-carbinol. The results were as follows.
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:9]1[C@@:13]2([CH3:28])[CH2:14][CH2:15][CH2:16]/[C:17](=[CH:18]\[CH:19]=[C:20]3\[CH2:21][C@@H:22]([OH:27])[CH2:23][CH2:24][C:25]\3=[CH2:26])/[C@@H:12]2[CH2:11][CH2:10]1)[CH2:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7].[Na].O.O[Si](O)(O)O.[Al].[Al]>>[CH3:26][C:25]1[CH2:24][CH2:23][C@H:22]([OH:27])[CH2:21][C:20]=1/[CH:19]=[CH:18]\[C:17]1[C@@H:12]2[CH2:11][CH2:10][C@H:9]([C@@H:2]([CH2:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7])[CH3:1])[C@@:13]2([CH3:28])[CH2:14][CH2:15][CH:16]=1
Reactant: C=C1CC[C@H](O)C/C1=C/C=C1\CCC[C@]2(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@@H]12
Agent: O[Si](O)(O)O
Agent: [Al]
Agent: [Na]
Solvent: O
Product: CC1=C(/C=C\C2=CCC[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@@H]23)C[C@@H](O)CC1
Reaction time: 2 h

Procedure:
A 2% loading of 7-dehydrocholesterol on mordenite with a Si:Al ratio of 5.2-6 in the sodium form (Valfor C500-11 from PQ) was treated in the same was as in Example 6. After 120 min., a significant amount of previtamin D3 was formed, but there was very little tachysterol formed.
Reaction SMILES: C(O)(=O)C.[CH3:5][C:6]1[C:12]2=[C:13]3[C:17](=[CH:18][CH:19]=[C:11]2[O:10][CH2:9][CH2:8][N:7]=1)[N:16]([S:20]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)(=[O:22])=[O:21])[CH:15]=[CH:14]3.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:5][CH:6]1[C:12]2=[C:13]3[C:17](=[CH:18][CH:19]=[C:11]2[O:10][CH2:9][CH2:8][NH:7]1)[N:16]([S:20]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)(=[O:22])=[O:21])[CH:15]=[CH:14]3
Reactant: CC1=NCCOc2ccc3c(ccn3S(=O)(=O)c3ccccc3)c21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: CC1NCCOc2ccc3c(ccn3S(=O)(=O)c3ccccc3)c21
Reaction time: 0.5 h
Yield: 37.2 %

Procedure:
1,1′-Azobis(N,N-dimethylformamide) (73 mg, 0.43 mmol) was added to a solution of 1-[5-hydroxy-1-(phenylsulfonyl)-1H-indol-4-yl]ethanone (Intermediate 23, 67 mg, 0.21 mmol), tert-butyl N-(2-hydroxy-ethyl)carbamate (0.14 g, 0.85 mmol) and triphenylphosphine (112 mg, 0.430 mmol) in DCM (5 mL). The mixture was heated at 43° C. for 1 hour and additional 1,1′-azobis(N,N-dimethylformamide) (0.030 g, 0.17 mmol) was added and the mixture was heated at 43° C. for an additional 2 hours. The mixture was cooled to room temperature and TFA (2.5 mL) was added and the mixture was stirred for 1 hour and evaporated. The residue was partitioned between DCM and 1 M NaOH. The organic phase was dried (MgSO4) and evaporated. The crude product was purified by flash chromatography using 5% MeOH in DCM as the eluent to give 75 mg of 1-methyl-8-(phenylsulfonyl)-3,8-dihydro-4H-[1,4]oxazepino[6,7-e]indole. Acetic acid (132 mg, 2.20 mmol) was added to a solution of the 1-methyl-8-(phenylsulfonyl)-3,8-dihydro-4H-[1,4]oxazepino[6,7-e]indole (75.0 mg, 0.22 mmol) in DCM (10 mL) and the mixture was allowed to stir for 10 minutes at room temperature before sodium triacetoxyborohydride (0.070 g, 0.33 mmol) was added all in one portion. The mixture was stirred for 30 minutes and transferred to a separation funnel and washed with 1 M NaOH and brine. The organic phase was dried (MgSO4) and evaporated. The crude product was purified by flash chromatography on silica gel using MeOH:DCM:NEt3 (5:94:1) as the eluent to give the title compound (28 mg) as a white solid. MS m/z 343 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:3]=1[CH2:4][N:5]1[C:17]2[CH:16]=[N:15][C:14]([C:18]([NH:20][NH2:21])=[O:19])=[CH:13][C:12]=2[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2.[C:27]([C:30]1[CH:38]=[CH:37][C:33]([C:34]([OH:36])=[O:35])=[CH:32][CH:31]=1)(=O)[CH3:28].CS(C)=O>C(O)(=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:3]=1[CH2:4][N:5]1[C:17]2[CH:16]=[N:15][C:14]([C:18]([NH:20][N:21]=[C:27]([C:30]3[CH:38]=[CH:37][C:33]([C:34]([OH:36])=[O:35])=[CH:32][CH:31]=3)[CH3:28])=[O:19])=[CH:13][C:12]=2[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2
Reactant: NNC(=O)c1cc2c3ccccc3n(Cc3cc(Cl)ccc3Cl)c2cn1
Reactant: CC(=O)c1ccc(C(=O)O)cc1
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Solvent: CS(C)=O
Product: CC(=NNC(=O)c1cc2c3ccccc3n(Cc3cc(Cl)ccc3Cl)c2cn1)c1ccc(C(=O)O)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 73 %

Procedure:
A mixture of 9-(2,5-dichlorobenzyl)-9H-β-carboline-3-carbohydrazide (100 mg, 0.25 mmole), 4-acetyl benzoic acid (50 mg, 0.3 mmole), DMSO (5 mL), and one drop of glacial acetic acid was stirred at room temperature for 12 hours. Ethyl acetate (50 ml) was added to the flask. The mixture was extracted with water and brine. The product crystallized from the organic phase was filtered, affording 97 mg (73%) of the title compound. 1H NMR (DMSO-d6) δ9.0 (s, 2H), 8.5 (d, 1H), 8.25 (s, 1H), 8.0-7.9 (m, 4H), 7.6-7.5 (m, 3H), 7.4-7.3 (m, 2H), 6.6 (s, 1H), 5.9 (s, 2H), 2.4 (s, 3H),MS (APCI; (M+H)+) m/z 531.
Reaction SMILES: [OH:1][N:2]=[C:3]([C:5]1[CH:10]=[CH:9][N:8]=[N:7][CH:6]=1)[NH2:4].[F:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[C:15](Cl)=O.N>>[F:11][C:12]1[CH:13]=[C:14]([C:15]2[O:1][N:2]=[C:3]([C:5]3[CH:10]=[CH:9][N:8]=[N:7][CH:6]=3)[N:4]=2)[CH:18]=[CH:19][CH:20]=1
Reactant: NC(=NO)c1ccnnc1
Reactant: O=C(Cl)c1cccc(F)c1
Agent: N
Product: Fc1cccc(-c2nc(-c3ccnnc3)no2)c1

Procedure:
The titled compound was prepared according to the procedure of Method D using the product of Example 83D and 3-fluorobenzoyl chloride (Aldrich). 1H NMR (300 MHz, CD3OD) δ 7.45-7.53 (m, 1 H), 7.69 (td, J=8.1, 5.6 Hz, 1 H), 8.00 (ddd, J=9.1, 2.6, 1.4 Hz, 1 H), 8.11 (dt, J=7.9, 1.2 Hz, 1 H), 8.39 (dd, J=5.4, 2.2 Hz, 1 H), 9.45 (dd, J=5.2, 1.2 Hz, 1 H), 9.87 (dd, J=2.2, 1.4 Hz, 1 H) ppm; MS (DCI/NH3) m/z=243 (M+H)+.