Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]1[C@H:8]([CH3:9])[CH2:7][CH2:6][CH2:5][N:4]1[C:10]([C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:13]=1[N:19]1[N:23]=[CH:22][CH:21]=[N:20]1)=[O:11].Cl[C:25]1[C:32]([F:33])=[CH:31][C:28]([C:29]#[N:30])=[CH:27][N:26]=1>>[F:33][C:32]1[C:25]([NH:1][CH2:2][C@@H:3]2[C@H:8]([CH3:9])[CH2:7][CH2:6][CH2:5][N:4]2[C:10](=[O:11])[C:12]2[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:13]=2[N:19]2[N:23]=[CH:22][CH:21]=[N:20]2)=[N:26][CH:27]=[C:28]([CH:31]=1)[C:29]#[N:30]
Reactant: N#Cc1cnc(Cl)c(F)c1
Reactant: Cc1ccc(-n2nccn2)c(C(=O)N2CCC[C@@H](C)[C@H]2CN)c1
Product: Cc1ccc(-n2nccn2)c(C(=O)N2CCC[C@@H](C)[C@H]2CNc2ncc(C#N)cc2F)c1

Procedure:
The title compound was prepared following the same general protocol as described for Example A1, using ((2S,3R)-2-(aminomethyl)-3-methylpiperidin-1-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone and 6-chloro-5-fluoronicotinonitrile. ESI-MS (m/z): 434 [M+1]+.
Reaction SMILES: [CH2:1]([C:6]12[CH2:17][CH2:16][CH2:15][C:13]3[C:14]1=[C:9]([CH:10]=[CH:11][CH:12]=3)[NH:8][C:7]2=[O:18])[CH2:2][CH2:3][CH:4]=C.C[N+]1([O-])CC[O:23]CC1.O1CCOCC1.I([O-])(=O)(=O)=O.[Na+]>[Os](=O)(=O)(=O)=O.O>[CH:4]([CH2:3][CH2:2][CH2:1][C:6]12[CH2:17][CH2:16][CH2:15][C:13]3[C:14]1=[C:9]([CH:10]=[CH:11][CH:12]=3)[NH:8][C:7]2=[O:18])=[O:23]
Reactant: C=CCCCC12CCCc3cccc(c31)NC2=O
Reactant: C[N+]1([O-])CCOCC1
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Solvent: C1COCCO1
Product: O=CCCCC12CCCc3cccc(c31)NC2=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.8 %

Procedure:
In a shaded container, 2a-(4-pentenyl)-2a,3,4,5-tetrahydrobenz[cd]indole-2(1H)-one (1.3 g, 5.3 mmol) and N-methylmorpholine oxide (1.9 g, 16 mmol) were dissolved in a mixed solvent of 1,4-dioxane (20 ml) and water (10 ml), and the resulting solution was mixed with osmium tetroxide (4% aqueous solution 3.4 ml, 0.53 mmol) and stirred at a room temperature for 2 hours. The reaction solution was mixed with water (80 ml), and then the reaction product was extracted with ethyl acetate, washed with saturated brine and dried with anhydrous sodium sulfate. Then the solvent was evaporated under a reduced pressure. The thus obtained residue was dissolved in a mixed solvent of 1,4-dioxane (20 ml) and water (10 ml). The resulting solution was mixed with sodium periodate (2.6 g, 12 mmol) and stirred for 2.5 hours as such. Water (100 ml) was added to the reaction solution, and the reaction product was extracted with ethyl acetate, washed with saturated brine and dried with anhydrous sodium sulfate. By evaporating the solvent from the resulting extract under a reduced pressure, 1.3 g of the title compound was obtained (5.3 mmol, 100% in yield).
Reaction SMILES: Cl.[C:2]1([N:8]([CH2:34][CH2:35][C:36]([O:38]CC)=[O:37])[C:9]([C:11]2[CH:33]=[CH:32][C:14]3[N:15]([CH:29]4[CH2:31][CH2:30]4)[C:16]([CH2:18][NH:19][C:20]4[CH:25]=[CH:24][C:23]([C:26](=[NH:28])[NH2:27])=[CH:22][CH:21]=4)=[N:17][C:13]=3[CH:12]=2)=[O:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>>[C:2]1([N:8]([CH2:34][CH2:35][C:36]([OH:38])=[O:37])[C:9]([C:11]2[CH:33]=[CH:32][C:14]3[N:15]([CH:29]4[CH2:30][CH2:31]4)[C:16]([CH2:18][NH:19][C:20]4[CH:25]=[CH:24][C:23]([C:26](=[NH:27])[NH2:28])=[CH:22][CH:21]=4)=[N:17][C:13]=3[CH:12]=2)=[O:10])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cc1)n2C1CC1)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: N=C(N)c1ccc(NCc2nc3cc(C(=O)N(CCC(=O)O)c4ccccc4)ccc3n2C2CC2)cc1
Yield: 64 %

Procedure:
Prepared analogously to Example 26 from 1-cyclopropyl-2-[N-(4-amidinophenyl)aminomethyl]benzimidazol-5-yl-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)amide hydrochloride and sodium hydroxide solution. Yield: 64% of theory, C28H28N6O3 (496.6); EKA mass spectrum: (M+H)+=497; (M+H+Na)++=260; (M+Na)+=519; (M+2Na)++=271.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][N+:7]3[CH2:20][CH2:19][C:18]4[C:13](=[CH:14][C:15]5[O:23][CH2:22][O:21][C:16]=5[CH:17]=4)[C:8]=3[CH:9]=2)[C:4]=1[O:24][CH3:25].[Cl-].[C:27]1([Mg]Cl)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(OCC)C>[CH3:25][O:24][C:4]1[C:5]2[CH:6]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:7]3[CH2:20][CH2:19][C:18]4[C:13]([C:8]3=[CH:9][C:10]=2[CH:11]=[CH:12][C:3]=1[O:2][CH3:1])=[CH:14][C:15]1[O:23][CH2:22][O:21][C:16]=1[CH:17]=4
Reactant: COc1ccc2cc3[n+](cc2c1OC)CCc1cc2c(cc1-3)OCO2
Reactant: Cl[Mg]c1ccccc1
Agent: [Cl-]
Solvent: CCOCC
Product: COc1ccc2c(c1OC)C(c1ccccc1)N1CCc3cc4c(cc3C1=C2)OCO4
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 67.2 %

Procedure:
To a suspension of berberine hydrochloride (400 mg, 1.08 mmol) in anhydrous diethyl ether (50 mL) at 0° C. was added phenylmagnesium chloride solution (2.8 mL, 2.7 mmol) dropwise. After stirring at 0° C. for 10 min, the reaction was quenched by adding saturated aqueous ammonium chloride solution (20 mL). The mixture was extracted with diethyl ether (2×50 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was re-crystallized from diethyl ether to afford 9,10-dimethoxy-8-phenyl-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline (300 mg, 67%). LC/MS m/e calcd for C26H23NO4 (M+H)+: 414.48, observed: 414.2; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.67-2.90 (m, 3 H) 3.35-3.41 (m, 1 H) 3.49 (s, 3 H) 3.74 (s, 3 H) 5.70 (s, 1 H) 5.99 (d, J=1.52 Hz, 2 H) 5.98 (s, 1 H) 6.72 (s, 1 H) 6.80 (m, 1 H) 6.88 (m, 1 H) 7.16-7.28 (m, 4 H) 7.35 (d, J=7.07 Hz, 2 H).
Reaction SMILES: [CH3:1][N:2]1[C:10]([CH2:11][CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([N:24]1[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]=[C:25]1[CH3:33])=[N:6][C:7]=2[N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.Br[CH:35]([CH3:39])[C:36]([NH2:38])=[O:37]>>[CH3:1][N:2]1[C:10]([CH2:11][CH:12]2[CH2:17][CH2:16][N:15]([C@@H:35]([CH3:39])[C:36]([NH2:38])=[O:37])[CH2:14][CH2:13]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([N:24]1[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]=[C:25]1[CH3:33])=[N:6][C:7]=2[N:18]1[CH2:19][CH2:20][O:21][CH2:22][CH2:23]1
Reactant: CC(Br)C(N)=O
Reactant: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CC3CCNCC3)n(C)c2n1
Product: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CC3CCN([C@@H](C)C(N)=O)CC3)n(C)c2n1

Procedure:
Following General Procedure C, 4-(9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-(piperidin-4-ylmethyl)-9H-purin-6-yl)morpholine and 2-bromopropionamide were reacted to give the racemic mixture. The enantiomers were separated by SFC to give 560. LCMS m/z: 259.7 (2M+H+)
Reaction SMILES: Cl.[CH3:2][O:3][C:4]([C:6]1[N:7]([CH2:24][CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[C:8](=[O:23])[C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:13][C:12]([Br:22])=[CH:11][CH:10]=2)=[O:5].C(N(CC)CC)C.[C:38]1(=[O:44])[O:43][C:41](=[O:42])[CH2:40][CH2:39]1>O1CCCC1>[CH3:2][O:3][C:4]([C:6]1[N:7]([CH2:24][CH:25]2[CH2:30][CH2:29][N:28]([C:38](=[O:44])[CH2:39][CH2:40][C:41]([OH:43])=[O:42])[CH2:27][CH2:26]2)[C:8](=[O:23])[C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:13][C:12]([Br:22])=[CH:11][CH:10]=2)=[O:5]
Reactant: COC(=O)c1c(-c2ccccc2)c2cc(Br)ccc2c(=O)n1CC1CCNCC1
Reactant: O=C1CCC(=O)O1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COC(=O)c1c(-c2ccccc2)c2cc(Br)ccc2c(=O)n1CC1CCN(C(=O)CCC(=O)O)CC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 85 %

Procedure:
To a solution of 6-bromo-1-oxo-4-phenyl-2-(piperidin-4-ylmethyl)-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester hydrochloride (100 mg) in tetrahydrofuran (5 ml) were added triethylamine (0.14 ml) and succinic anhydride (30 mg), and the mixture was stirred at room temperature for 24 hrs. The solvent was evaporated under reduced pressure, water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried by adding sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was crystallized from isopropyl ether to give the title compound (96 mg, 81%).
Reaction SMILES: [CH3:1][C:2]([O:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=1[C:11]([OH:13])=[O:12])=[O:3].C(=O)([O-])[O-].[Ca+2:18]>O>[CH3:1][C:2]([O:4][C:5]1[C:10]([C:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[CH3:1][C:2]([O:4][C:5]1[C:10]([C:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[Ca+2:18]
Reactant: CC(=O)Oc1ccccc1C(=O)O
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: O
Product: CC(=O)Oc1ccccc1C(=O)[O-]

Procedure:
A stock solution of calcium aspirin is prepared by mixing 4.032 gm of aspirin and 1.120 gm of precipitated calcium carbonate with 50 ml of distilled water at 40°-50° C. until the solids are completely dissolved, then diluting to 60 ml with distilled water at ambient temperature to obtain a solution containing 67.2 mg/ml of aspirin equivalent. All dosing solutions are prepared by dilution of the stock solution with distilled water; the vehicle control is distilled water. All solutions are used within two hours of preparation, then discarded.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:18]([O:20]C)=[O:19])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:6][N:7]=1.[Li+].[OH-].O.Cl>CO>[NH2:1][C:2]1[C:3]([C:18]([OH:20])=[O:19])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:6][N:7]=1
Reactant: COC(=O)c1nc(-c2ccc(S(C)(=O)=O)cc2)cnc1N
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CS(=O)(=O)c1ccc(-c2cnc(N)c(C(=O)O)n2)cc1
Temperature: 90 °C
Yield: 99.4 %

Procedure:
A mixture of methyl 3-amino-6-(4-(methylsulfonyl)phenyl)pyrazine-2-carboxylate (3.50 g, 11.39 mmol) and LiOH (1.364 g, 56.95 mmol) was dissolved in Methanol (14 mL) and water (14 ml) and allowed to heat at 90° C. for 2 hours. The reaction mixture was allowed to cool and neutralized with 1M HCl. The resultant precipitate was collected by filtration to afford the pure product as a yellow solid (3.32 g, 99% Yield). MS (ES+) 293
Reaction SMILES: [NH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][C:6](=[O:11])[C:5]=2[CH:4]=[CH:3][C:2]1=[O:12].[CH2:13](Br)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1(C)C=CC=CC=1>[CH2:13]([O:12][C:2]1[CH:3]=[CH:4][C:5]2[C:6](=[O:11])[CH2:7][CH2:8][CH2:9][C:10]=2[N:1]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C1CCCc2[nH]c(=O)ccc21
Reactant: BrCc1ccccc1
Solvent: Cc1ccccc1
Product: O=C1CCCc2nc(OCc3ccccc3)ccc21
Temperature: 25 °C
Reaction time: 72 h
Yield: 92 %

Procedure:
A mixture of 7,8-dihydro-1H,6H-quinoline-2,5-dione (20.4 g, 125.0 mmoL), benzyl bromide (17.8 mL, 150 mmoL) and 20.8 g, 75 mmoL) in toluene (250 mL) was stirred at room temperature for 3 days under the protection from light. The reaction was stopped, filtered through celite and rinsed with a mixture of methylene chloride and methanol. The filtrate was concentrated and trituated in petroleum ether (150 mL). Filtration of the mixture provided the desired product (29.4 g, 92%).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([S:30][CH3:31])=[N:19][N:20]3[C:23]3[CH:24]=[C:25]([CH3:29])[CH:26]=[CH:27][CH:28]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C>Cl.O1CCOCC1>[CH3:31][S:30][C:18]1[C:17]2[C:21](=[CH:22][C:14]([C:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH:10]=3)=[CH:15][CH:16]=2)[N:20]([C:23]2[CH:24]=[C:25]([CH3:29])[CH:26]=[CH:27][CH:28]=2)[N:19]=1
Reactant: CSc1nn(-c2cccc(C)c2)c2cc(C3=CCN(C(=O)OC(C)(C)C)CC3)ccc12
Agent: Cl
Solvent: C1COCCO1
Product: CSc1nn(-c2cccc(C)c2)c2cc(C3=CCNCC3)ccc12

Procedure:
A solution of 4-(3-methylsulfanyl-1-m-tolyl-1H-indazol-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (22.5 mg, 0.052 mmol) in 4 N HCl in 1,4-dioxane (3 mL) was stirred at room temperature for 1 h, then concentrated. The resulting residue was triturated and sonicated in a mixture of MeOH (0.5 mL)/diethyl ether (5 mL). The resulting mixture was filtered to yield the title compound as a yellowish solid.
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11](=[O:15])[O:12][CH2:13][CH3:14].[I:18]I>C1CCCCC1.C1COCC1>[I:18][C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([O:3][C:2]([F:16])([F:17])[F:1])[C:5]=1[NH:10][C:11](=[O:15])[O:12][CH2:13][CH3:14]
Reactant: II
Reactant: CCOC(=O)Nc1ccccc1OC(F)(F)F
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: CCOC(=O)Nc1c(I)cccc1OC(F)(F)F
Reaction time: 1 h
Yield: 73 %

Procedure:
A 1.4 M solution of sec-butyllithiuni in cyclohexane (3.0 mL) was added drop-wise to a solution of ethyl N-[2-(trifluoromethoxy)phenyl]carbamate (0.5000 g, 0.002006 mol) in THF (9 mL) at −70° C. After stirring for 1 hour a solution of iodine (0.51 g, 0.002 mol) in THF (1.0 mL) was added drop-wise at −70° C. Stirring was continued for another 1 hour then the mixture was quenched with saturated ammonium chloride solution. Water (50 mL) was added and the mixture extracted with diethyl ether (3×40 mL). The combined organic phases was washed with 40% sodium meta-bisulfite solution, water and brine, then dried over Na2SO4 and the solvent removed in vacuo to give the desired product in a 73% yield. 1H NMR (400 MHz, CDCl3): δ 1.29-1.36 (m, 3H), 4.21-4.28 (m, 2H), 6.21 (br, 1H), 7.05 (t, J=8.0 Hz, 1H), 7.30 (m, 1H) and 7.80 (dd, J=6.8, 1.2 Hz, 1H). MS (ES+): m/z 375.78 [MH+].
Reaction SMILES: [CH3:1][C:2]1[C:16]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:15]([C:21]([F:24])([F:23])[F:22])[CH:14]=[CH:13][C:3]=1[C:4]([NH:6][C:7]1[N:11]([CH3:12])[N:10]=[N:9][N:8]=1)=[O:5].I[CH2:26][CH3:27].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[CH2:26]([N:6]([C:7]1[N:11]([CH3:12])[N:10]=[N:9][N:8]=1)[C:4](=[O:5])[C:3]1[CH:13]=[CH:14][C:15]([C:21]([F:24])([F:22])[F:23])=[C:16]([S:17]([CH3:20])(=[O:19])=[O:18])[C:2]=1[CH3:1])[CH3:27]
Reactant: Cc1c(C(=O)Nc2nnnn2C)ccc(C(F)(F)F)c1S(C)(=O)=O
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCN(C(=O)c1ccc(C(F)(F)F)c(S(C)(=O)=O)c1C)c1nnnn1C
Temperature: 80 °C
Reaction time: 16 h

Procedure:
100 mg (0.275 mmol) of 2-methyl-3-(methylsulfonyl)-N-(1-methyl-1H-tetrazol-5-yl)-4-(trifluoromethyl)benzamide and 43 mg (0.275 mmol) of iodoethane are dissolved in 5 ml of N,N-dimethylformamide, and 0.038 mg (0.275 mmol) of potassium carbonate is added. The reaction mixture is stirred at 80° C. for 16 h and taken up in 5 ml of water and extracted twice with 10 ml each time of dichloromethane. The organic phase is dried over Na2SO4 and concentrated. The residue is purified by means of preparative HPLC (acetonitrile, water). Yield 30 mg (26%).
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH2:8][S+:9]([O-:19])[C:10]2[NH:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[N:18]=2)=[N:6][CH:5]=[CH:4][C:3]=1[O:20][CH2:21][CH2:22][CH2:23][O:24][CH3:25].[OH-].[Na+:27].C>C1COCC1>[CH3:1][C:2]1[C:7]([CH2:8][S+:9]([O-:19])[C:10]2[N-:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[N:18]=2)=[N:6][CH:5]=[CH:4][C:3]=1[O:20][CH2:21][CH2:22][CH2:23][O:24][CH3:25].[Na+:27]
Reactant: COCCCOc1ccnc(C[S+]([O-])c2nc3ccccc3[nH]2)c1C
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COCCCOc1ccnc(C[S+]([O-])c2nc3ccccc3[n-]2)c1C
Temperature: 27.5 °C
Reaction time: 0.5 h

Procedure:
Rabeprazole (10 g) was suspended in 30 ml THF and sodium hydroxide solution (1.11 g sodium hydroxide dissolved in 1 ml water) was added at 25-30° C. Reaction mass was stirred for 30 minutes at 25-30° C. Added activated charcoal (1.0 g) and stirred for 30 minutes at 25-30° C. Filtered and washed charcoal bed with THF (20 ml). Distilled out THF under reduced pressure at 30-35° C. completely. Residue was dissolved in THF (20 ml). In a separate R B flask charged n-heptane (100 ml) at 25° C. Added slowly above reaction mass in 15-20 minutes at 25-30° C. Stirred at 25-30° C. for 2 hours. The product was filtered off under nitrogen atmosphere and wet cake was washed with n-heptane (2×20 ml). Dried under vacuum at 50° C. for 20-24 hours to obtain amorphous Rabeprazole sodium.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[O:12]1[C:16]2[CH:17]=[CH:18][C:19]([C:21]3([C:24]([NH:26][C:27]4[CH:28]=[N:29][C:30]([CH3:34])=[C:31](Br)[CH:32]=4)=[O:25])[CH2:23][CH2:22]3)=[CH:20][C:15]=2[O:14][CH2:13]1.O1C2C=CC(C3(C(NC4C=NC(C)=C(C5C=CC=CC=5)C=4)=O)CC3)=CC=2OC1>>[O:12]1[C:16]2[CH:17]=[CH:18][C:19]([C:21]3([C:24]([NH:26][C:27]4[CH:28]=[N:29][C:30]([CH3:34])=[C:31]([C:5]5[CH:6]=[CH:7][CH:8]=[C:3]([CH2:2][OH:1])[CH:4]=5)[CH:32]=4)=[O:25])[CH2:23][CH2:22]3)=[CH:20][C:15]=2[O:14][CH2:13]1
Reactant: Cc1ncc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)cc1Br
Reactant: OCc1cccc(B(O)O)c1
Agent: Cc1ncc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)cc1-c1ccccc1
Product: Cc1ncc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)cc1-c1cccc(CO)c1

Procedure:
1-(Benzo[d][1,3]dioxol-5-yl)-N-(5-(3-(hydroxymethyl)phenyl)-6-methylpyridin-3-yl)cyclopropanecarboxamide was prepared from 3-(hydroxymethyl)phenylboronic acid and 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-bromo-6-methylpyridin-3-yl)cyclopropanecarboxamide in a manner analogous to that of 1-(benzo[d][1,3]dioxol-5-yl)-N-(6-methyl-5-phenylpyridin-3-yl)cyclopropanecarboxamide.
Reaction SMILES: [CH3:1][C:2]([CH3:37])([CH3:36])[CH2:3][CH2:4][N:5]1[C:10](=[O:11])[C:9]([C:12]2[NH:17][C:16]3[CH:18]=[CH:19][C:20]([NH:22][S:23]([CH3:26])(=[O:25])=[O:24])=[CH:21][C:15]=3[S:14](=[O:28])(=[O:27])[N:13]=2)=[C:8]([OH:29])[CH:7]2[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH:6]12.[C:38](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O>[CH3:1][C:2]([CH3:37])([CH3:36])[CH2:3][CH2:4][N:5]1[C:10](=[O:11])[C:9]([C:12]2[NH:17][C:16]3[CH:18]=[CH:19][C:20]([N:22]([CH3:38])[S:23]([CH3:26])(=[O:24])=[O:25])=[CH:21][C:15]=3[S:14](=[O:28])(=[O:27])[N:13]=2)=[C:8]([OH:29])[CH:7]2[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH:6]12
Reactant: CC(C)(C)CCN1C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)C2CCCCCCC21
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CN(c1ccc2c(c1)S(=O)(=O)N=C(C1=C(O)C3CCCCCCC3N(CCC(C)(C)C)C1=O)N2)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 63.9 %

Procedure:
N-{3-[1-(3,3-Dimethyl-butyl)-4-hydroxy-2-oxo-1,2,4a,5,6,7,8,9,10,10a-decahydro-cycloocta[b]pyridin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (prepared as described in Example 35b, 0.20 g, 0.36 mmol) was dissolved in N,N-dimethylformamide (12 mL). Potassium carbonate (0.10 g, 0.72 mmol) and iodomethane (0.025 mL, 0.40 mmol) were added sequentially. The reaction was stirred at 25° C. for 3 h. The reaction was quenched via the addition of 1.0 M aqueous hydrochloric acid solution (20 mL). The mixture was extracted with ethyl acetate (3×30 mL). The organic layers were combined and washed with saturated aqueous brine solution (20 mL) before they were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a golden oil. Purification by flash column chromatography (Teledyne Isco RediSep Flash Column 12 g; 0-20% ethyl acetate in dichloromethane) afforded the desired product, N-{3-[1-(3,3-dimethyl-butyl)-4-hydroxy-2-oxo-1,2,4a,5,6,7,8,9,10,10a-decahydro-cycloocta[b]pyridin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-N-methyl-methanesulfonamide (0.018 g, 0.23 mmol, 9%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.00-1.02 (9H, m), 1.35-1.80 (14H, m), 2.87-2.88 (3H, m), 3.00-3.35 (2H, m), 3.36-3.38 (3H, m), 3.86-4.15 (2H, m), 7.20-7.28 (1H, m), 7.64-7.79 (2H, m). LC-MS (ESI) calcd for C26H38N4O6S2 566.73, found 567.4 [M+H+].
Reaction SMILES: [CH:1]12[CH2:11][CH2:10][CH:7]([CH:8]=[CH:9]1)[CH:6]1[CH:2]2[C:3](=[O:13])[O:4][C:5]1=[O:12]>C(OCC)(=O)C.[Pd]>[CH:7]12[CH2:8][CH2:9][CH:1]([CH2:11][CH2:10]1)[CH:2]1[CH:6]2[C:5](=[O:12])[O:4][C:3]1=[O:13]
Reactant: O=C1OC(=O)C2C3C=CC(CC3)C12
Agent: [Pd]
Solvent: CCOC(C)=O
Product: O=C1OC(=O)C2C3CCC(CC3)C12
Temperature: 25 °C
Reaction time: 16 h
Yield: 72.2 %

Procedure:
4-Oxa-tricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (4.00 g, 22.45 mmol) was dissolved in ethyl acetate (100 mL). 10% Palladium on carbon (400 mg) was added. The flask was degassed and backfilled with hydrogen gas via balloon. The mixture was stirred at 25° C. for 16 h. The mixture was passed through a plug of Celite and the filtrate was concentrated in vacuo to afford a thick clear oil. Purification by flash column chromatography (Teledyne Isco RediSep column; 0 to 30% ethyl acetate in hexanes) afforded the desired product, 4-oxa-tricyclo[5.2.2.02,6]undecane-3,5-dione (2.92 g, 16.20 mmol, 72%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.55-1.64 (6H, m), 1.76 (2H, d, J=9.2 Hz), 2.25 (2H, s), 3.11 (2H, s). LC-MS (ESI) calcd for C10H12O3 180.20, found 181.0 [M+H+].
Reaction SMILES: [F:1][C:2]([F:53])([F:52])[C:3]1[CH:4]=[C:5]([CH:45]=[C:46]([C:48]([F:51])([F:50])[F:49])[CH:47]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[C:39]([O:40][CH3:41])=[CH:38][CH:37]=[C:36]([C:42]([CH3:44])=[CH2:43])[N:35]=1)[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:10][N:9]=1>C(O)C.[C].[Pd]>[F:53][C:2]([F:1])([F:52])[C:3]1[CH:4]=[C:5]([CH:45]=[C:46]([C:48]([F:51])([F:50])[F:49])[CH:47]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[C:39]([O:40][CH3:41])=[CH:38][CH:37]=[C:36]([CH:42]([CH3:43])[CH3:44])[N:35]=1)[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][N:13]=1
Reactant: C=C(C)c1ccc(OC)c(-c2ccc(C(F)(F)F)cc2CN(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ncc(OCCCC(=O)OCC)cn2)n1
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CCCOc1cnc(N(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)Cc2cc(C(F)(F)F)ccc2-c2nc(C(C)C)ccc2OC)nc1
Reaction time: 1.5 h
Yield: 91.9 %

Procedure:
Ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(6-isopropenyl-3-methoxy-pyridin-2-yl)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate (76 mg) is dissolved in ethanol (5 ml), and thereto is added 10% palladium-carbon (15 mg) and the mixture is stirred under hydrogen atmosphere for 1.5 hours. The catalyst is removed by filtration, and the filtrate is concentrated under reduced pressure to give ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(6-isopropyl-3-methoxy-pyridin-2-yl)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate (70 mg). MS (m/z): 759 [M+H]+
Reaction SMILES: C[O:2][C:3](=[O:28])[CH:4]([N:11]1[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH2:25][CH2:26][OH:27])[CH:13]=[N:12]1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.Cl>O1CCOCC1>[CH:6]1([CH2:5][CH:4]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH2:25][CH2:26][OH:27])[CH:13]=[N:12]2)[C:3]([OH:28])=[O:2])[CH2:10][CH2:9][CH2:8][CH2:7]1
Reactant: COC(=O)C(CC1CCCC1)n1ncc(Oc2ccccc2CCO)cc1=O
Agent: Cl
Solvent: C1COCCO1
Product: O=C(O)C(CC1CCCC1)n1ncc(Oc2ccccc2CCO)cc1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 41.9 %

Procedure:
A solution of 3-cyclopentyl-2-{4-[2-(2-hydroxy-ethyl)-phenoxy]-6-oxo-6H-pyridazin-1-yl}-propionic acid methyl ester (386 mg, 1 mmol) in dioxane (5 mL) was treated with a 6N aqueous hydrochloric acid solution (5 mL). The reaction solution was stirred at 25° C. overnight and then concentrated in vacuo. Chromatography afforded 3-cyclopentyl-2-{4-[2-(2-hydroxy-ethyl)-phenoxy]-6-oxo-6H-pyridazin-1-yl}-propionic acid (156 mg, 42%); LC-MS: 373 (M+1)+, tR=3.28 min. Purity on HPLC: tR=5.98 min, 97.9% (214 nm), 96.5% (254 nm). 1H NMR (300 MHz, DMSO-d6): δ12.95 (s, 1H, broad), 8.14 (s, 1H), 7.46-7.20 (m, 4H), 6.37 (d, 1H, J=2.7 Hz), 5.31 (dd, 1H, J=10.5 Hz, J=4.5 Hz), 4.70 (t, 1H, J=5.4 Hz), 3.59-3.52 (m, 2H), 3.66 (t, J=6.6 Hz, 1H), 2.17-1.97 (m, 2H), 1.58-1.01 (m, 9H).