Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:19])([S:15]([O-:18])(=[O:17])=[O:16])[CH:3]([O:8][C:9](=[O:14])[C:10](C)([CH3:12])[CH3:11])[C:4]([F:7])([F:6])[F:5].[CH2:20]([NH+:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[CH3:21].O.[Na].C(N(CC)CC)C.C(OC(=O)C(C)=C)(=O)C(C)=C.Cl>CO.CN(C)C1C=CN=CC=1.C(#N)C>[F:19][C:2]([F:1])([S:15]([O-:18])(=[O:16])=[O:17])[CH:3]([O:8][C:9](=[O:14])[C:10]([CH3:12])=[CH2:11])[C:4]([F:5])([F:7])[F:6].[CH2:20]([NH+:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[CH3:21]
Reactant: CC(C)(C)C(=O)OC(C(F)(F)F)C(F)(F)S(=O)(=O)[O-]
Agent: C=C(C)C(=O)OC(=O)C(=C)C
Agent: CC[NH+](CC)CC
Agent: CN(C)c1ccncc1
Solvent: CC#N
Solvent: O
Solvent: CO
Product: C=C(C)C(=O)OC(C(F)(F)F)C(F)(F)S(=O)(=O)[O-]
Reaction time: 8 h

Procedure:
Triethylammonium 1,1,3,3,3-pentafluoro-2-(pivaloyloxy)propane-1-sulfonate prepared by the method disclosed in Japanese Patent Laid-Open (kokai) No. 2007-304490 is dissolved in methanol and 2 equivalents of 25 wt % aqueous solution of sodium hydrate was added thereto. After confirming a separation of a pivaloyloxy group by 19F-NMR, 2.1 equivalents of 12N hydrochloric acid was added and both methanol and water were removed by evaporation under reduced pressure, and then ethyl ether was added to the obtained residue to perform recrystallization. The crude substance containing sodium chloride was filtrated and then triethylamine (1.5 equivalents), 4-dimethylamino pyridine (0.025 equivalent) and acetonitrile (4 fold of the crude substance by weight) were added and the mixture was iced-cooled. Then, methacrylic acid anhydride (1.0 equivalent) was dropped and the mixture was stirred overnight. 3N hydrochloric acid was added to the reaction solution to make the solution acidic, and acetonitrile was removed by evaporation under reduced pressure at low temperature, and thereafter, the solution was dissolved in dichloromethane and then washed by water. After dichloromethane was removed by evaporation under reduced pressure, the obtained crude substance was used for the next reaction without purification.
Reaction SMILES: [CH3:1][N:2]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.S(=O)(=O)(O)O.[N+:32]([O-])([OH:34])=[O:33]>>[CH2:9]([N:2]([CH3:1])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:8]=1[N+:32]([O-:34])=[O:33])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: O=[N+]([O-])O
Reactant: CCCCCCCCCCCCCCCCCCN(C)c1ccccc1
Agent: O=S(=O)(O)O
Product: CCCCCCCCCCCCCCCCCCN(C)c1ccccc1[N+](=O)[O-]
Temperature: 0 °C

Procedure:
Add 23.6 g (0.22 mol) N-methylaniline into 92 g (0.2 mol) 14% hexane solution of N-butyllithium and stir it for 10-20 minutes. Add 33.3 g (0.1 mol) octadecylbromide into the above solution, while stirring it. Add 200 ml water into the solution, after heating and refluxing the solution for about 17 hours and cooling it down to room temperature. Add 6N hydrochloric acid to the solution after concentrating the solution extracted by 300 ml diethyl ether and deposit it. 32.3 g (0.09 mol) N, N-methyloctadecyl-aniline is obtained by refinement through crystaiization with ethyl alcohol and water. Dissolve the obtained 32.3 g (0.09 mol) N, N-methyloctadecyl-aniline into 250 ml concentrated sulfuric acid. Add 30 ml concentrated nitric acid into the solution while stirring it in an ice water bath. Leave it about one hour after adding the nitric acid. Add the solution into ice water, filter off the deposit from it, and refine it by crystallization with ethyl alcohol and water. With the above step, 14.5 g (0.036 mol) N, N-octadecylmethyl-o -nitroaniline is obtained. Add 100 ml 2N hydrochloric acid into this 14.5 g (0.036 mol) N, N-octadecylmethyl-o-nitroaniline which is dissolved into 200 ml ethyl alcohol. 11.7 g (0.031 mol) N, N-octadecylmethyl-o-phenylene-diamine is obtained after adding 11.75 (0.18 mol) zinc dust into the above solution to be heated and refluxed for one hour.
Reaction SMILES: [CH2:1]1[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH:6]=[CH:5][CH:4]=[C:3]3[CH2:2]1.C(O)(=[O:15])C>O.O.O.O.O.O.[Co](Br)Br.O.O.O.O.C([O-])(=O)C.[Co+2].C([O-])(=O)C.O.O.O.O.C([O-])(=O)C.[Mn+2].C([O-])(=O)C>[C:2]1(=[O:15])[C:3]2=[C:12]3[C:7](=[CH:6][CH:5]=[CH:4]2)[CH:8]=[CH:9][CH:10]=[C:11]3[CH2:1]1
Reactant: CC(=O)O
Reactant: c1cc2c3c(cccc3c1)CC2
Agent: Br[Co]Br
Agent: [Co+2]
Agent: [Mn+2]
Solvent: O
Product: O=C1Cc2cccc3cccc1c23
Reaction time: 4.3 h
Yield: 28.1 %

Procedure:
To a three necked flask of 10 L, 308 g of acenaphthene, 3250 mL of acetic acid, 30.6 g of cobalt (II) bromide hexahydrate, 6.1 g of cobalt (II) acetate tetrahydrate, and 1.5 g of manganese (II) acetate tetrahydrate were put. These components were stirred and mixed to be dissolved totally. Then, air was blown into the liquid at a rate of 400 L/h at 20° C. and room pressure. After 4.3 hours, the reaction was stopped, and the generated reaction solution was analyzed by gas chromatography. As a result, it was found that the acenaphthene inversion rate was 99.2% and the acenaphthene-1-one yield was 28.1%.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[C:14]3[C:15]([CH3:22])=[C:16]([OH:21])[C:17]([CH3:20])=[C:18]([CH3:19])[C:13]=3[O:12][C:11]2([CH3:24])[CH3:23])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[C:25]1([CH2:31][CH2:32]O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[C:14]3[C:15]([CH3:22])=[C:16]([O:21][CH2:32][CH2:31][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:17]([CH3:20])=[C:18]([CH3:19])[C:13]=3[O:12][C:11]2([CH3:24])[CH3:23])=[CH:6][CH:5]=1)([CH3:3])[CH3:2]
Reactant: Cc1c(C)c2c(c(C)c1O)C(c1ccc(C(C)C)cc1)C(C)(C)O2
Reactant: OCCc1ccccc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1c(C)c2c(c(C)c1OCCc1ccccc1)C(c1ccc(C(C)C)cc1)C(C)(C)O2
Yield: 11.4 %

Procedure:
A solution of 3-(4-isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-ol (1.0 g, 3.08 mmol), 2-phenylethanol (414 mg, 3.39 mmol), triphenylphosphine (890 mg, 3.39 mmol) and diethyl azodicarboxylate (590 mg, 3.39 mmol) in tetrahydrofuran (20 mL) was stirred for 30 minutes at room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (hexane/ethyl acetate=100/1) to obtain the title compound (150 mg, yield 11%).
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[CH:11]1([NH:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:15][CH2:14][CH2:13][CH2:12]1.P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:16]([CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21]2)[CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15]2)=[O:8])=[CH:4][N:3]=1
Reactant: C1CCC(NC2CCCC2)C1
Reactant: Cc1ccc(C(=O)O)cn1
Solvent: Cc1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Product: Cc1ccc(C(=O)N(C2CCCC2)C2CCCC2)cn1
Temperature: 25 °C
Yield: 44.1 %

Procedure:
To a suspension of 6-methylnicotinic acid (1.37 g, 10 mmol) in toluene (10 ml), N,N-dicyclopentylamine (1.84 g, 12 mmol) was added To the homogenous solution obtained, phosphorus oxychloride (0.23 mL, 12 mmol) was injected in dropwise fashion. The reaction mixture was then immersed in an oil-bath at 130° C. and refluxed for 8 h. The reaction flask was cooled and stirred at room temperature. After 16h, the reaction was quenched with water and extracted in ethyl acetate. The organic layer was successively washed with aq. potassium carbonate, water and brine. After drying (MgSO4), the solvent was removed. The crude product (2.5 g) was chromatographed (silica gel, ethyl acetate/acetonitrile 100/1.5) to give the title compound (1.2 g, 44%). IR (KBr)1625, 1590, 1450, 1430, 1375, 1340, 1290, 1130, 840, 750 cm-1 ; 1H NMR (CDCl3) 1.4-2.35 (m, 16H), 2.57 (s, 3H), 3.6-3.9 (m,2H), 7.17 (d, J=8 Hz, 1H), 7.6 (dd,J=3,8 Hz, 1H), and 8.5 ppm (d,J=3 Hz,1H).
Reaction SMILES: Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]([C:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([C:21]4[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:22]=4[O:29][CH2:30][CH:31]4[CH2:33][CH2:32]4)[C:15]=3[NH:14][C:13]=2[CH3:34])=[O:11])[CH2:5][CH2:4]1.[C:35](Cl)(=[O:38])[CH2:36][CH3:37]>>[CH:31]1([CH2:30][O:29][C:22]2[CH:23]=[CH:24][C:25]([O:27][CH3:28])=[CH:26][C:21]=2[C:20]2[C:15]3[NH:14][C:13]([CH3:34])=[C:12]([C:10]([NH:9][C@H:6]4[CH2:7][CH2:8][C@@H:3]([NH:2][C:35](=[O:38])[CH2:36][CH3:37])[CH2:4][CH2:5]4)=[O:11])[C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:32][CH2:33]1
Reactant: CCC(=O)Cl
Reactant: COc1ccc(OCC2CC2)c(-c2ncnc3c(C(=O)N[C@H]4CC[C@@H](N)CC4)c(C)[nH]c23)c1
Agent: Cl
Product: CCC(=O)N[C@H]1CC[C@@H](NC(=O)c2c(C)[nH]c3c(-c4cc(OC)ccc4OCC4CC4)ncnc23)CC1

Procedure:
Starting from N-(cis-4-aminocyclohexyl)-4-[2-(cyclopropylmethoxy)-5-methoxyphenyl]-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-7-carboxamide hydrochloride (example D.f25) and commercially available propionyl chloride the title compound is obtained as colorless solid.
Reaction SMILES: S(Cl)([Cl:3])=O.[C:5]1([CH3:28])[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([CH3:12])[C:6]=1[NH:13][C:14]1[S:15][C:16]2[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][C:20]([CH2:26]O)=[CH:19][C:17]=2[N:18]=1.O.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[Cl:3][CH2:26][C:20]1[CH:21]=[C:22]([N+:23]([O-:25])=[O:24])[C:16]2[S:15][C:14]([NH:13][C:6]3[C:7]([CH3:12])=[CH:8][C:9]([CH3:11])=[CH:10][C:5]=3[CH3:28])=[N:18][C:17]=2[CH:19]=1
Reactant: O=S(Cl)Cl
Reactant: Cc1cc(C)c(Nc2nc3cc(CO)cc([N+](=O)[O-])c3s2)c(C)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClC(Cl)Cl
Product: Cc1cc(C)c(Nc2nc3cc(CCl)cc([N+](=O)[O-])c3s2)c(C)c1
Temperature: 60 °C
Reaction time: 24 h
Yield: 64.3 %

Procedure:
Thionyl chloride (0.191 ml, 2.62 mmol) was added to a solution of (2-mesitylamino-7-nitro-1,3-benzothiazol-5-yl)methanol (180 mg, 0.524 mmol) in chloroform. The mixture was stirred at room temperature for 18 h and at 60° C. for 24h. The mixture was poured into water and neutralized with saturated NaHCO3 solution. The aqueous solution was extracted with AcOEt. The extract was washed with brine, dried over magnesium sulfate and concentrated under vacuum. The residue was purified by chromatography eluting with 20% AcOEt in n-hexane to afford 122 mg of the title compound.
Reaction SMILES: [CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:53])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([O:51][CH3:52])[CH2:45]2)[CH:7]([CH3:54])[CH:6]([O:55][Si:56]([C:59]([CH3:62])([CH3:61])[CH3:60])([CH3:58])[CH3:57])[CH2:5][C:4]1=[O:63])[CH3:2].ClC(Cl)(Cl)C(=N)O[CH2:68][CH:69]=[CH2:70].FC(F)(F)S(O)(=O)=O>C(Cl)Cl.C1CCCCC1.C(OCC)(=O)C>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:53])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][CH2:70][CH:69]=[CH2:68])[CH:46]([O:51][CH3:52])[CH2:45]2)[CH:7]([CH3:54])[CH:6]([O:55][Si:56]([C:59]([CH3:60])([CH3:61])[CH3:62])([CH3:58])[CH3:57])[CH2:5][C:4]1=[O:63])[CH3:2]
Reactant: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(O)C(OC)C3)C(C)C(O[Si](C)(C)C(C)(C)C)CC1=O)C(C)CC2OC
Reactant: C=CCOC(=N)C(Cl)(Cl)Cl
Agent: O=S(=O)(O)C(F)(F)F
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: C1CCCCC1
Product: C=CCOC1CCC(C=C(C)C2OC(=O)C3CCCCN3C(=O)C(=O)C3(O)OC(C(OC)CC(C)CC(C)=CC(CC)C(=O)CC(O[Si](C)(C)C(C)(C)C)C2C)C(OC)CC3C)CC1OC
Temperature: 25 °C
Reaction time: 24 h
Yield: 47 %

Procedure:
To a solution of 17-ethyl-1-hydroxy-14-(tert -butyldimethylsiloxy)-12-[2'-(4"-hydroxy-3"-methoxy -cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]-octacos-18-ene-2,3,10,16-tetraone (2.1 g) (STEP 11B) in 24 ml 33% methylene chloride in cyclohexane, was added allyl trichloroacetimidate (938 mg neat) and the reaction mixture was allowed to mix for 5 minutes. Trifluoromethanesulfonic acid (41 μl neat) was added slowly via syringe and the mixture stirred at room temperature. After 24 hours, the reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate, water and brine. The organic layer was dried over magnesium sulfate. Purification of the concentrate by flash chromatography on silica gel (ethyl acetate: hexane (1:5))+1% methanol) gave the title compound (1.03 g). 1H NMR consistent with the desired structure.
Reaction SMILES: [CH:1]1[C:14]2[C:13](=[N:15][NH:16][C:17]([NH2:19])=[S:18])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:20]([O-])(=O)[CH3:21].[Na+].ClCC=O>CO>[S:18]1[CH:21]=[CH:20][N:19]=[C:17]1[NH:16][N:15]=[C:13]1[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[NH:6][C:5]2[C:14]1=[CH:1][CH:2]=[CH:3][CH:4]=2
Reactant: NC(=S)NN=c1c2ccccc2[nH]c2ccccc12
Reactant: CC(=O)[O-]
Agent: O=CCCl
Agent: [Na+]
Solvent: CO
Product: c1ccc2c(=NNc3nccs3)c3ccccc3[nH]c2c1

Procedure:
6.24 g of 9-acridanone thiosemicarbazone, 3.5 g of sodium acetate and 5.2 ml of chloroacetaldehyde (50 percent aqueous solution) in 200 ml of methanol are heated to boiling under reflux for 6 hours. After evaporation of the solvent, the residue is treated with water. The precipitated product is filtered and washed successively with water, a small amount of ethanol, ether and petroleum ether. There is obtained 9-acridanone (2-thiazolyl)hydrazone of melting point 208°-210° (decomposition).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.[CH3:21][O:22]/[N:23]=[C:24](/[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)\[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33]O)=[CH:29][CH:28]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.C(OCC)(=O)C>[CH3:21][O:22]/[N:23]=[C:24](/[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)\[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][O:1][C:2]2[CH:3]=[CH:4][C:5]([CH:8]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=2)=[CH:29][CH:28]=1
Reactant: CO/N=C(\COc1ccc(CO)cc1)c1ccccc1
Reactant: CCOC(=O)CC(c1ccccc1)c1ccc(O)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCOC(=O)CC(c1ccccc1)c1ccc(OCc2ccc(OC/C(=N\OC)c3ccccc3)cc2)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 52.17 %

Procedure:
To a 100 mL of two neck RB flask was charged ethyl 3-(4-hydroxyphenyl)-3-phenylpropanoate (0.6 g, 2.2 mmol) and (4-{[(2Z)-2-(methoxyimino)-2-phenylethyl]oxy}phenyl)methanol (0.6 g, 2.2 mmol) in 20 mL of THF. To this added triphenyl phosphine (0.755 g, 2.88 mmol) at 0° C. and added DIAD (0.59 g, 2.88 mmol) portion wise over a period of 15 min at 0° C. After 12 h of stirring at RT, the mixture was diluted with Ethyl acetate, washed with water and brine solution successively. Organic phase was dried over anhydrous Na2SO4 and concentrated to afford yellow oil as product (0.6 g, yield: 52.17%); 1H NMR (300 MHz, DMSO-d6): δ 7.57-7.60 (m, 2H), 7.06-7.31 (m, 12H), 6.84-6.86 (m, 4H), 5.12 (s, 2H), 4.84 (s, 2H), 4.39-4.45 (t, 1H), 3.86-4.01 (m, 5H), 2.92-2.95 (d, 2H), 1.00-1.05 (t, 3H).
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:11][C:12]1[CH:13]=[CH:14][C:15]2[O:26][C:25]3[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=3[C@H:18]3[C:19](=O)[N:20]([CH3:22])[CH2:21][C@@H:17]3[C:16]=2[CH:31]=1.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[Na+]>O1CCCC1>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]2[O:26][C:25]3[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=3[C@H:18]3[CH2:19][N:20]([CH3:22])[CH2:21][C@@H:17]3[C:16]=2[CH:31]=1
Reactant: CN1C[C@@H]2c3cc(Cl)ccc3Oc3ccccc3[C@H]2C1=O
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [Al+3]
Agent: [Cl-]
Solvent: C1CCOC1
Product: CN1C[C@@H]2c3ccccc3Oc3ccc(Cl)cc3[C@H]2C1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 94.4 %

Procedure:
Aluminum chloride (65.7 mg) was added in portions to tetrahydrofuran (5 mL) at 0° C. Under stirring a 10% solution of lithium aluminum hydride in tetrahydrofuran (1.35 mL) was slowly added while keeping the temperature below 10° C. The mixture was cooled to 0° C. and stirred for 15 minutes. A solution of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrol-1-one (VII) (0.40 grams) in tetrahydrofuran (4 mL) was added to the mixture while keeping the temperature below 15° C. Stirring was continued for 2 hours at 10° C., whereupon 0.5 N sodium tartrate solution (15 mL) was added while keeping the temperature below 10° C. Stirring was continued for 15 minutes at 20° C. The salt layer was extracted twice with a toluene:ethyl acetate (8:2) mixture (25 mL). The combined organic layers were dried on magnesium sulphate, filtered and evaporated in vacuo to yield 0.36 grams (94%) of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole (A).
Reaction SMILES: O.O.[Sn](Cl)Cl.[CH:6]1([C:12]2[C:13]3[CH:14]=[CH:15][C:16]4[C:17](=[O:60])[NH:18][CH2:19][CH2:20][CH:21]=[CH:22][CH2:23][CH2:24][NH:25][C:26](=[O:59])[CH2:27][N:28]([C:57]=3[CH:58]=4)[C:29]=2[C:30]2[CH:35]=[CH:34][C:33]([O:36][CH2:37][C:38]3[CH:43]=[C:42]([N+:44]([O-])=O)[CH:41]=[CH:40][C:39]=3[N:47]3[CH2:52][CH2:51][N:50]([S:53]([CH3:56])(=[O:55])=[O:54])[CH2:49][CH2:48]3)=[CH:32][CH:31]=2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1>C1COCC1.C(O)C>[CH:6]1([C:12]2[C:13]3[CH:14]=[CH:15][C:16]4[C:17](=[O:60])[NH:18][CH2:19][CH2:20][CH:21]=[CH:22][CH2:23][CH2:24][NH:25][C:26](=[O:59])[CH2:27][N:28]([C:57]=3[CH:58]=4)[C:29]=2[C:30]2[CH:35]=[CH:34][C:33]([O:36][CH2:37][C:38]3[CH:43]=[C:42]([NH2:44])[CH:41]=[CH:40][C:39]=3[N:47]3[CH2:48][CH2:49][N:50]([S:53]([CH3:56])(=[O:54])=[O:55])[CH2:51][CH2:52]3)=[CH:32][CH:31]=2)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1
Reactant: CS(=O)(=O)N1CCN(c2ccc([N+](=O)[O-])cc2COc2ccc(-c3c(C4CCCCC4)c4ccc5cc4n3CC(=O)NCCC=CCCNC5=O)cc2)CC1
Agent: Cl[Sn]Cl
Solvent: C1CCOC1
Solvent: CCO
Solvent: O
Product: CS(=O)(=O)N1CCN(c2ccc(N)cc2COc2ccc(-c3c(C4CCCCC4)c4ccc5cc4n3CC(=O)NCCC=CCCNC5=O)cc2)CC1
Temperature: 25 °C

Procedure:
Tin(II) chloride dihydrate (400 mg, 1.77 mmol) was added to a solution of 3 (55 mg, 0.0715 mmol) in THF (1 mL) and ethanol (1.5 mL). The reaction mixture was heated at reflux for 3 days, then allowed to cool down to room temperature. Then, volatiles were evaporated under vacuum and the residue was successively partitioned between a diluted solution of NaHCO3 and ethyl acetate, dried (Na2SO4) and evaporated. Purification by column chromatography (CH2Cl2/methanol, 97.5:2.5) afforded the title compound 4 as a yellowish powder: m/z=740 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH2:11][S:12][C:13]2[NH:17][C:16]3[CH:18]=[CH:19][C:20]([O:22][CH3:23])=[CH:21][C:15]=3[N:14]=2)=[N:4][CH:5]=[C:6]([CH3:10])[C:7]=1[O:8][CH3:9].[OH-].[Na+].[O-:26]S([O-])(=S)=O.[Na+].[Na+].C(O)(=O)C>CO.O.OO>[CH3:10][C:6]1[CH:5]=[N:4][C:3]([CH2:11][S+:12]([O-:26])[C:13]2[NH:17][C:16]3[CH:18]=[CH:19][C:20]([O:22][CH3:23])=[CH:21][C:15]=3[N:14]=2)=[C:2]([CH3:1])[C:7]=1[O:8][CH3:9]
Reactant: O=S([O-])([O-])=S
Reactant: COc1ccc2[nH]c(SCc3ncc(C)c(OC)c3C)nc2c1
Agent: OO
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc2[nH]c([S+]([O-])Cc3ncc(C)c(OC)c3C)nc2c1
Reaction time: 0.5 h
Yield: 88 %

Procedure:
2 g of 2-[[(3,5-dimethyl-4-methoxy-2-pyridinyl)methyl]thio]-5-methoxy-1H-benzimidazole was suspended in 36 ml of methanol at room temperature, to which 1.88 g of 45% NaOH in 14 ml water was added while stirring. 0.09 g of Na2WO4·2H2O oxidation catalyst was dissolved in 0.74 g H2O2 (50% aqueous solution), and further diluted with 10 ml. of water. The oxidant/catalyst solution was added to the reactant/base solution dropwise so that the addition was completed in about 30 minutes while stirring at room temperature. The reaction was continued for additional 10 minutes while stirring. 10 ml of 10% Na2S2O3 aqueous solution was then added, and the resulting mixture was subjected to a reduced pressure to remove methanol therefrom. Finally, a precipitate was formed after adding a diluted acetic acid aqueous solution to a pH value of about 8, which was filtered, water washed, and dried in vacuo to obtain Omeprazole with a yield of about 88% (LC purity>95%).
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:26][CH:27]([C:33](=[O:35])[CH3:34])[C:28]([O:30][CH2:31][CH3:32])=[O:29].[C:36](O)(=[O:39])[CH2:37][CH3:38].CN1CCOCC1>CN(C=O)C.C1COCC1.O>[O:35]=[C:33]([CH3:34])[CH:27]([NH:26][C:36](=[O:39])[CH2:37][CH3:38])[C:28]([O:30][CH2:31][CH3:32])=[O:29]
Reactant: CCC(=O)O
Reactant: CCOC(=O)C(N)C(C)=O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Product: CCOC(=O)C(NC(=O)CC)C(C)=O
Reaction time: 1 h
Yield: 11.8 %

Procedure:
HATU (1.41 g, 3.7 mmol) was added to a mixture of ethyl 2-amino-3-oxobutanoate hydrochloride (565 mg, 3.12 mmol) and propionic acid (280 uL, 3.7 mmol) in DMF (2 mL) and THF (4 mL) at RT under N2. The reaction was stirred for 1 h and 4-methylmorpholine (0.41 mL, 3.7 mmol) was then added dropwise via a syringe pump to the above mixture. The reaction was stirred for 1 h and water was then added. It was extracted with EtOAc. The organic layer was washed with saturated sodium bicarbonate, HCl (1 N) and brine, dried over sodium sulfate and concentrated. The residue was purified by ISCO FC with 0-40% EtOAc in hexane to give the title compound (74 mg, 12%) as a light-yellow solid. 1H NMR (400 MHz, CDCl3-d) δ ppm 6.61 (s, 1H) 5.20 (d, J=6.59 Hz, 1H) 4.22 (q, J=7.14 Hz, 2H) 2.34 (s, 3H) 2.26 (q, J=7.51 Hz, 2H) 1.25 (t, J=7.14 Hz, 3H) 1.11 (t, J=7.51 Hz, 3H).
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]3[NH:31][N:30]=[N:29][N:28]=3)=[CH:17][CH:16]=2)[C:7]([C:11]([OH:13])=[O:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4].C(N(CC)CC)C.[C:39](Cl)([C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>ClCCl>[CH2:1]([C:5]1[N:6]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]3[N:31]([C:39]([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)([C:52]4[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=4)[C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=4)[N:30]=[N:29][N:28]=3)=[CH:17][CH:16]=2)[C:7]([C:11]([OH:13])=[O:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(Cl)c(C(=O)O)n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCc1nc(Cl)c(C(=O)O)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a dichloromethane (4.5 L) solution of 2-butyl-4-chloro-1-{[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid (235 g, 0.54 mol) was added triethylamine (85 mL, 0.59 mol), followed by a dichloromethane (800 mL) solution of trityl chloride (159 g, 0.56 mol), and the reaction mixture was stirred at room temperature overnight. The reaction mixture was washed with water, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Chromatography over silica eluting with 20-80% acetone/heptane afforded the title compound as an orange solid.