Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])/[CH:5]=[N:6]/[OH:7].[Cl:14]N1C(=O)CCC1=O>CN(C)C=O>[OH:7]/[N:6]=[C:5](\[Cl:14])/[C:4]1[CH:8]=[CH:9][C:10]([N+:11]([O-:13])=[O:12])=[C:2]([CH3:1])[CH:3]=1
Reactant: O=C1CCC(=O)N1Cl
Reactant: Cc1cc(/C=N/O)ccc1[N+](=O)[O-]
Solvent: CN(C)C=O
Product: Cc1cc(/C(Cl)=N/O)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a solution of (E)-3-methyl-4-nitrobenzaldehyde oxime (1.0 equiv.) in dimethylformamide, N-chlorosuccinimide (1.2 equiv.) was added in 3 portions over the period of 1 hr and the reaction mixture was stirred at r.t. for 5 hours. DMF was evaporated and the residue was diluted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel, eluting with 5% ethyl acetate in petroleum ether (60-80), to provide the title compound as a creamish solid (78%); 1H NMR (300 MHz, DMSO-d6) δ: 2.55 (s, 3H), 7.81-7.84 (d, J=8.7 Hz, 2H), 7.86 (s, 1H), 8.04-8.07 (d, J=8.4 Hz, 1H), 12.86 (s, 1H); IR (KBr) 3320, 3105, 2925, 1607, 1583, 1521, 1440, 1387, 1358, 1310, 1259, 1183, 1010, 860 cm−1.
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]1[O:8][CH2:7][C@@H:6]([N:9]2[C:13]3=[C:14]4[S:20][CH:19]=[CH:18][C:15]4=[N:16][CH:17]=[C:12]3[N:11]=[C:10]2[C@H:21]([OH:23])[CH3:22])[CH2:5][CH2:4]1.C(N(CC)C(C)C)(C)C.[CH3:33][S:34](Cl)(=[O:36])=[O:35]>CO>[OH:23][C@@H:21]([C:10]1[N:9]([C@@H:6]2[CH2:7][O:8][C@@H:3]([CH2:2][NH:1][S:34]([CH3:33])(=[O:36])=[O:35])[CH2:4][CH2:5]2)[C:13]2=[C:14]3[S:20][CH:19]=[CH:18][C:15]3=[N:16][CH:17]=[C:12]2[N:11]=1)[CH3:22]
Reactant: C[C@@H](O)c1nc2cnc3ccsc3c2n1[C@H]1CC[C@H](CN)OC1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CO
Product: C[C@@H](O)c1nc2cnc3ccsc3c2n1[C@H]1CC[C@H](CNS(C)(=O)=O)OC1
Reaction time: 0.5 h
Yield: 36.9 %

Procedure:
To a solution of (1R)-1-{1-[(3S,6R)-6-(aminomethyl)tetrahydro-2H-pyran-3-yl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl}ethanol (11 mg, 0.033 mmol) in methanol (0.5 mL) was added N,N-diisopropylethylamine (17 μL, 0.099 mmol) and methanesulfonyl chloride (2.8 μL, 0.036 mmol). After stirring for 0.5 h, another equivalent of methanesulfonyl chloride was added. After stirring for 20 min, The reaction solution was diluted with methanol and purified with prep-LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (5 mg, 37%). LCMS calculated for C17H23N4O4S2 (M+H)+: m/z=411.1. Found: 411.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([NH2:8])=[O:7].[H-].[Na+].C[O:15][CH2:16][CH2:17]OC>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:6]2[O:7][CH2:17][C:16](=[O:15])[N:8]=2)[CH:9]=[CH:10][CH:11]=1
Reactant: COc1cccc(C(N)=O)c1
Reactant: COCCOC
Agent: [H-]
Agent: [Na+]
Product: COc1cccc(C2=NC(=O)CO2)c1
Temperature: 110 °C
Reaction time: 0.5 h
Yield: 26 %

Procedure:
2 g (1 eq) of 3-methoxybenzamide was mixed with 3.1 ml (2.7 eq) of chloroacethylchloride and the resulting mixture was heated at 110° C. for 1 h. After cooling, the resulting solid was recrystallized in CHCl3. The resulting solid was added to a suspension of NaH (489 mg, 1.1 eq) in DME at 0° C. After 30 min, the resulting mixture was refluxed for 5 h, cooled to RT and hydrolyzed, extracted with AcOEt, washed with NaCl salt and dried. The resulting solid was recrystallized in a mixture hexane/AcOEt giving 16 as a white solid in 26% yield.
Reaction SMILES: C(OC([NH:8][C@H:9]([C:22]([N:24]([CH3:42])[C@@H:25]([C:30]([NH:32][CH2:33][CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:31])[CH2:26][CH2:27][S:28][CH3:29])=[O:23])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17]C(C)(C)C)=[CH:13][CH:12]=1)=O)(C)(C)C.C(OCC)(=O)C.[ClH:49]>>[ClH:49].[NH2:8][C@H:9]([C:22]([N:24]([CH3:42])[C@@H:25]([C:30]([NH:32][CH2:33][CH2:34][CH2:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:31])[CH2:26][CH2:27][S:28][CH3:29])=[O:23])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1
Reactant: CSCC[C@H](C(=O)NCCCc1ccccc1)N(C)C(=O)[C@H](Cc1ccc(OC(C)(C)C)cc1)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: CCOC(C)=O
Product: CSCC[C@H](C(=O)NCCCc1ccccc1)N(C)C(=O)[C@@H](N)Cc1ccc(O)cc1

Procedure:
A solution of [N-(tert-butyloxycarbonyl)-O-(tert-butyl)-L-tyrosyl]-N2 -methyl-N-(3-phenylpropyl)-D-methioninamide (1.81 g.) in hydrogen chloride-ethyl acetate (3.4 N, 20 ml.) was stirred for one hour at room temperature, then stripped of volatiles. The product was crystallized from isopropyl alcohol, affording L-tyrosyl-N2 -methyl-N-(3-phenylpropyl)-D-methioninamide monohydrochloride (966 mg.; m.r. 208°-210° C.; [α]D25 +85.7°, c=1, methanol), whose free base is the compound of Formula II wherein Q is Met, R1 and R5 are each hydrogen, R2 is methyl and R4 is (CH2)nY wherein n is 3 and Y is phenyl.
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][NH2:4].[CH2:5]1[O:7][CH:6]1[CH2:8][Cl:9].Cl.[C:11](=[O:14])([OH:13])[O-:12].[Na+]>O>[CH2:1]=[CH:2][CH2:3][NH3+:4].[CH2:5]1[O:7][CH:6]1[CH2:8][Cl:9].[C:11]([O-:14])([OH:13])=[O:12]
Reactant: C=CCN
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCC1CO1
Product: C=CC[NH3+]
Temperature: 62.5 °C
Reaction time: 4 h
Yield: 79.5 %

Procedure:
Sevelamer hydrochloride (1.1 Kg) was added into 15.5 L solution of sodium bicarbonate (1.1 Kg NaHCO3 in 14.3 L water). The obtained mixture was stirred at 60-65° C. for 4 hrs. The obtained material was filtered by centrifuge filter. The obtained wet cake was added into 15.5 L solution of sodium bicarbonate (1.1 Kg NaHCO3 in 14.3 L water) and stirring was maintained at 60-65° C. for 4 hrs. The material was filtered by centrifuge filter assembly and obtained wet cake was stirred in 11 L water for 1 hr at 60-65° C. The material was filtered by centrifuge filter. The washings of the wet cake with water were repeated thrice at 60-65° C. The obtained wet cake was dried in air tray dryer (ATD) at about 90-100° C. for 30-36 hrs and LOD was checked after every five hours till LOD was in the range of 5 to 10% to get Sevelamer carbonate (0.995 Kg).
Reaction SMILES: [C:1]([C:9]1[S:13][C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=2[C:10]=1[OH:18])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[CH3:23][CH:24]([CH3:27])[CH2:25][NH3+:26]>>[CH3:23][CH:24]([CH3:27])[CH2:25][NH:26]/[C:1](/[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[C:9]1\[C:10](=[O:18])[C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[S:13]\1
Reactant: CC(C)C[NH3+]
Reactant: O=C(c1ccccc1)c1sc2ccccc2c1O
Agent: CC(=O)[O-]
Product: CC(C)CN/C(=C1/Sc2ccccc2C1=O)c1ccccc1
Yield: 69 %

Procedure:
Prepared as in Example 35 from 2-benzoyl-benzo[b]thiophen-3-ol and (2-methylpropyl)ammonium acetate with a yield of 69% of theory; m.p. 125°-126° C. (ethyl acetate/petroleum ether 1:2).
Reaction SMILES: [CH:1]1([O:4][C:5]2[CH:6]=[C:7]([C:15]3[NH:32][C:18]4[CH:19]=[N:20][N:21](COCC[Si](C)(C)C)[C:22](=[O:23])[C:17]=4[C:16]=3[C:33]3[CH:34]=[N:35][NH:36][CH:37]=3)[CH:8]=[CH:9][C:10]=2[O:11][CH:12]([F:14])[F:13])[CH2:3][CH2:2]1.C1(OC2C=C(C3NC4C=NN(COCC[Si](C)(C)C)C(=O)C=4C=3CCC)C=CC=2OC(F)F)CC1>>[CH:1]1([O:4][C:5]2[CH:6]=[C:7]([C:15]3[NH:32][C:18]4[CH:19]=[N:20][NH:21][C:22](=[O:23])[C:17]=4[C:16]=3[C:33]3[CH:34]=[N:35][NH:36][CH:37]=3)[CH:8]=[CH:9][C:10]=2[O:11][CH:12]([F:14])[F:13])[CH2:2][CH2:3]1
Reactant: C[Si](C)(C)CCOCn1ncc2[nH]c(-c3ccc(OC(F)F)c(OC4CC4)c3)c(-c3cn[nH]c3)c2c1=O
Agent: CCCc1c(-c2ccc(OC(F)F)c(OC3CC3)c2)[nH]c2cnn(COCC[Si](C)(C)C)c(=O)c12
Product: O=c1[nH]ncc2[nH]c(-c3ccc(OC(F)F)c(OC4CC4)c3)c(-c3cn[nH]c3)c12
Yield: 100.7 %

Procedure:
Reaction and post treatment were carried out in the same manner as in Example 6-(c) except for using 100 mg (0.189 mmol) of 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(4-pyrazolyl)-5-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Example 18-(b) in place of 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-propyl-5-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, whereby 76 mg of the title compound was obtained as a pale yellowish solid substantially quantitatively.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([NH2:7])=[O:6].[C:14](=O)([O-])[O-].[Cs+].[Cs+].S(OC)(OC)(=O)=O>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([NH:7][CH3:14])=[O:6]
Reactant: NC(=O)c1cc(F)cc([N+](=O)[O-])c1
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: COS(=O)(=O)OC
Solvent: CN(C)C=O
Product: CNC(=O)c1cc(F)cc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 74.3 %

Procedure:
To a solution of 3-fluoro-5-nitrobenzamide (1.0 g, 5.43 mmoL) in DMF (17 mL) was added cesium carbonate (2.6 g, 8.14 mmoL) and dimethyl sulphate (547 mg, 4.34 mmol) and the reaction mixture was stirred at RT for 24 h. The reaction mixture was concentrated under reduced pressure and extracted with EtOAc (2×40 ml). The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography provided 3-fluoro-N-methyl-5-nitrobenzamide (0.800 g, 80%) as a solid. Observed mass (M−1): 196.9.
Reaction SMILES: C[O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([NH:10][C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][N:6]1[C:19](=[O:29])[CH2:20][NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:4].[OH-].[Na+].Cl>CO>[C:11]([NH:10][C@H:8]1[CH2:7][N:6]([C:19](=[O:29])[CH2:20][NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[C@H:5]([C:3]([OH:4])=[O:2])[CH2:9]1)(=[O:18])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: COC(=O)[C@@H]1C[C@@H](NC(=O)c2ccccc2)CN1C(=O)CNC(=O)OC(C)(C)C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)NCC(=O)N1C[C@H](NC(=O)c2ccccc2)C[C@H]1C(=O)O
Temperature: -3 °C
Reaction time: 2.5 h
Yield: 100.1 %

Procedure:
To a solution of (2S,4R) methyl-4-benzamido-1-(2-(tert-butoxycarbonyl-amino)acetyl)pyrrolidine-2-carboxylate (23.33 g, 0.0575 mol) in methanol (450 mL) was added NaOH (0.2875 mol, 144 mL of 2N aqueous solution) at −1 to 1° C. over 15 min. The mixture was stirred at −5 to −1° C. for 2.5 h. HCl (0.2875 mol, 144 mL of 2N aqueous solution) was added at −3 to 1° C. over 25 min. MeOH was distilled off under vacuum, then 500 mL of EtOAc was added. The aqueous phase was saturated with NaCl and the phases were separated. The aqueous phase was extracted with 2×250 mL EtOAc and the combined EtOAc solution was dried over MgSO4, and concentrated to afford 22.54 g of (2S,4R) 4-benzamido-1-(2-(tert-butoxycarbonylamino)acetyl)pyrrolidine-2-carboxylic acid as a white foamy solid (contains 6.6 wt % EtOAc; 94% yield adjusted to residual EtOAc). 1H NMR (CD3OD, δ, ppm): 7.87-7.79 (m, 2 H), 7.58-7.42 (m, 3 H), 4.81-4.7 (m 1 H), 4.69-4.56 (m, 1 H), 4.05-3.72 (m, 3 H), 3.67-3.49 (m, 1 H), 2.64-2.28 (m, 2 H), 1.43 (s, 9 H). MS (m/z, positive ESI) for M+H: 392; for M+Na: 414.
Reaction SMILES: [C:1]1([CH3:28])[CH:6]=[CH:5][C:4]([NH:7][C:8]2[CH:16]=[C:15]([C:17]([OH:19])=O)[C:14]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)=[CH:13][C:9]=2[C:10](O)=[O:11])=[CH:3][CH:2]=1>O>[CH3:27][C:24]1[CH:23]=[CH:22][C:21]2[NH:20][C:14]3[C:15]([C:17](=[O:19])[C:26]=2[CH:25]=1)=[CH:16][C:8]1[NH:7][C:4]2[CH:3]=[CH:2][C:1]([CH3:28])=[CH:6][C:5]=2[C:10](=[O:11])[C:9]=1[CH:13]=3
Reactant: Cc1ccc(Nc2cc(C(=O)O)c(Nc3ccc(C)cc3)cc2C(=O)O)cc1
Solvent: O
Product: Cc1ccc2[nH]c3cc4c(=O)c5cc(C)ccc5[nH]c4cc3c(=O)c2c1
Temperature: 130 °C
Yield: 99.5 %

Procedure:
To 150.0 g of polyphosphoric acid (118%) was added with stirring 30.0 g (79.7 mmol) of 2,5-bis(p-toluidino)terephthalic acid. The stirred mixture was irradiated in the microwave oven for 2.5 minutes. After the reaction mixture was cooled to 130° C., 250 g of water was slowly added with stirring. The resultant slurry was stirred for 30 minutes, after which the solid component was collected by filtration and washed with 6.0 liters of water. The presscake was dried overnight in an oven at 60° C. to give 27.0 g of crude 2,9-dimethylquinacridone (C. I. Pigment Red 122) (100% yield).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1.[CH3:12][N:13]=[C:14]=[S:15]>C(O)(C)C>[CH3:12][NH:13][C:14]([NH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1)=[S:15]
Reactant: CN=C=S
Reactant: NCCCNc1ccccn1
Solvent: CC(C)O
Product: CNC(=S)NCCCNc1ccccn1
Yield: 60.3 %

Procedure:
A solution of 2-(3-aminopropylamino)pyridine (2.74 g.) and methyl isothiocyanate (1.46 g.) in isopropyl alcohol (50 ml.) was stirred at room temperature for 16 hours Concentration, followed by trituration of the residue under methyl ethyl ketone gave the crude product which, was recrystallised from aqueous ethanol to give N-methyl-N'-[3-(2-pyridylamino)propyl]thiourea (2.45 g.) m.p. 134°-135.5°.
Reaction SMILES: N1C2C(=CC=CC=2)NC1=O.[N+:11]([C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[CH2:16][C:17](=[O:23])[NH:18]2)([O-])=O>>[NH2:11][C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[CH2:16][C:17](=[O:23])[NH:18]2
Reactant: O=C1Cc2c(cccc2[N+](=O)[O-])N1
Agent: O=c1[nH]c2ccccc2[nH]1
Product: Nc1cccc2c1CC(=O)N2

Procedure:
Essentially following the procedures described in Intermediate 4, but using 4-nitro-1,3-dihydro-2H-indol-2-one from Step A in place of 5-nitro-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one, the title compound was obtained. MS: m/z=149 (M+1).
Reaction SMILES: [CH2:1]([C@:3]1([OH:28])[C:25]2[CH:24]=[C:23]3[N:10]([CH2:11][C:12]4[C:13]3=[N:14][C:15]3[CH:16]=[C:17]([F:22])[CH:18]=[CH:19][C:20]=3[CH:21]=4)[C:9](=[O:26])[C:8]=2[CH2:7][O:6][C:5](=[O:27])[CH2:4]1)[CH3:2].[F:29][C:30]([F:36])([F:35])[CH2:31][CH2:32]C=O>>[CH2:1]([C@:3]1([OH:28])[C:25]2[CH:24]=[C:23]3[N:10]([CH2:11][C:12]4[C:13]3=[N:14][C:15]3[CH:16]=[C:17]([F:22])[CH:18]=[CH:19][C:20]=3[C:21]=4[CH2:32][CH2:31][C:30]([F:36])([F:35])[F:29])[C:9](=[O:26])[C:8]=2[CH2:7][O:6][C:5](=[O:27])[CH2:4]1)[CH3:2]
Reactant: O=CCCC(F)(F)F
Reactant: CC[C@@]1(O)CC(=O)OCc2c1cc1n(c2=O)Cc2cc3ccc(F)cc3nc2-1
Product: CC[C@@]1(O)CC(=O)OCc2c1cc1n(c2=O)Cc2c-1nc1cc(F)ccc1c2CCC(F)(F)F

Procedure:
The product of Example 2 is treated with 4,4,4-trifluorobutyraldehyde according to a procedure similar to Stage 13e in order to produce the expected solid.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7]([OH:9])[CH:6]=[CH:5][C:3]=1[OH:4].OO.C(N(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O)CN(CC([O-])=O)CC([O-])=O.[Na+].[Na+].[Na+].[Na+].[Na+].S(=O)(=O)(O)O>C(O)(=O)C>[CH3:1][C:2]1[C:3](=[O:4])[CH:5]=[CH:6][C:7](=[O:9])[CH:8]=1
Reactant: Cc1cc(O)ccc1O
Agent: O=C([O-])CN(CCN(CC(=O)[O-])CC(=O)[O-])CCN(CC(=O)[O-])CC(=O)[O-]
Agent: O=S(=O)(O)O
Agent: OO
Solvent: CC(=O)O
Product: CC1=CC(=O)C=CC1=O
Reaction time: 0.25 h
Yield: 89.3 %

Procedure:
A solution of 12.4 g (100 mmol) of methylhydroquinone in 90 ml of acetic acid and 28.4 g (250 mmol) of 30% by weight aqueous hydrogen peroxide were simultaneously added dropwise to a stirred solution of 0.68 g (2.0 mmol) of iron 5,14-dihydrodibenzo[b,i]-[5,9,14,18]tetraaza[14]annulene, 2.52 g (2.0 mmol) of a 40% by weight aqueous solution of pentasodium diethylenetriaminepentaacetate and 0.5 ml of concentrated sulfuric acid in 50 ml of acetic acid at 40° C. with cooling. The mixture was then stirred for 15 min and subsequently subjected to a steam distillation. The distillate was extracted three times with a total of 400 ml of methylene chloride. The organic phase was shaken with aqueous sodium bicarbonate solution and then with water, separated from the aqueous phase, dried over magnesium sulfate, filtered and evaporated to dryness to yield 10.9 g (89%) of methylbenzoquinone in the form of a yellow powder. Melting point 69°-71° C.
Reaction SMILES: CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Br:15][C:16]1[CH:17]=[N:18][NH:19][CH:20]=1.O[CH:22]1[CH2:27][CH2:26][CH2:25][N:24]([CH3:28])[CH2:23]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[Br:15][C:16]1[CH:17]=[N:18][N:19]([CH:22]2[CH2:27][CH2:26][CH2:25][N:24]([CH3:28])[CH2:23]2)[CH:20]=1
Reactant: CN1CCCC(O)C1
Reactant: Brc1cn[nH]c1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CN1CCCC(n2cc(Br)cn2)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
DIAD (3.21 ml, 16.3 ml) was added dropwise to a solution of 4-bromopyrazole (2.0 g, 13.6 mmol), 3-hydroxy-1-methylpiperidine (1.57 ml, 13.6 ml) and triphenylphosphine (4.3 g, 16.3 mmol) in THF (50 ml) at 0° C. The mixture was allowed to warm to room temperature and stirred overnight. The reaction was partitioned between water and ethyl acetate and the organic layers were extracted into 2N HCl. The aqueous fraction was basified with sodium bicarbonate and extracted into ethyl acetate. The organic fractions were dried (MgSO4), filtered and concentrated under reduced pressure to give the product (1.64 g), which was used without purification. MS: [M+H]+=244.
Reaction SMILES: C(O)[C@H]1O[C@H]([O:8][CH2:9][C@H:10]2[O:14][C:13]([OH:17])([CH2:15][OH:16])[C@@H:12]([OH:18])[C@@H:11]2[OH:19])[C@H](O)[C@@H](O)[C@@H]1O.C(O)[C@H]1O[C@H](OCC([C@@H](O)[C@H](O)[C@H](O)CO)=O)[C@H](O)[C@@H](O)[C@@H]1O.C(O)[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@](O)(CO)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O.O.C(O)[C@H]1O[C@H](O[C@@H]([C@H](O)C(CO)=O)[C@H](O)CO)[C@H](O)[C@@H](O)[C@@H]1O.C(O)[C@H]1O[C@H](O[C@@H]([C@@H](O)[C@H](O)C(CO)=O)CO)[C@H](O)[C@@H](O)[C@@H]1O>>[CH2:15]([OH:16])[C@@H:13]([OH:17])[C@@H:12]([OH:18])[C@H:11]([OH:19])[C@H:10]([OH:14])[CH2:9][OH:8]
Reactant: OC[C@H]1O[C@H](OC[C@H]2OC(O)(CO)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@@H]1O
Agent: O=C(CO)[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Agent: O=C(CO)[C@@H](O)[C@H](O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)[C@H](O)CO
Agent: O=C(CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: O
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
In another preferred embodiment, isomaltulose is hydrogenated. The composition of the reaction product here has a different composition than is expected from a conventional process, where about 50 wt.-% 1,1-GPM and 50 wt.-% 1,6-GPS are generated. The reaction product has a larger 1,1-GPM fraction and a smaller 1,6-GPS fraction. Advantageously, the process of the invention can also be used for hydrogenating trehalulose to 1,1-GPM and 1-0-α-D-glocupyranosil-D-sorbite (1,1-GPS), lactulose to lactite and 3-0-β-D-glucopyranosil-D-mannite, maltulose to 3-0-α-D-glucopyranosil-D-mannite and 4-0-α-D-glucopyranosil-D-sorbite (maltite), and leucrose to 5-0-α-D-glucopyranosil-D-sorbite (1,5-GPS) and 2-0-α-D-glocupyranosil-D-mannite (1,2-GPM). Advantageously, the product has a relatively higher 1,1-GPM fraction in the case of trehalulose, a relatively higher 3-0-α-D-glucopyranosil-D-mannite fraction in the case of maltulose, and a relatively higher 3-0-β-D-glucopyranosil-D-mannite fraction in the case of lactulose. When the aforedescribed glucopyranosil-substituted ketoses are hydrogenated, the invention thus produces an larger mannite epimer fraction and a smaller sorbite epimer fraction in the product.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[Cl:10][C:11]1[CH:12]=[C:13]([CH:15]=[CH:16][C:17]=1[CH3:18])[NH2:14]>>[NH2:14][C:13]1[CH:12]=[C:11]([Cl:10])[C:17]([CH3:18])=[CH:16][C:15]=1[C:4]([C:3]1[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=1[Cl:1])=[O:5]
Reactant: O=Cc1ccccc1Cl
Reactant: Cc1ccc(N)cc1Cl
Product: Cc1cc(C(=O)c2ccccc2Cl)c(N)cc1Cl

Procedure:
(2-amino-4-chloro-5-methylphenyl)-(2-chlorophenyl)-methanone (Xhh) was prepared by reacting 2-chlorobenzaldehyde with 0.0318 moles of 3-chloro-4-methyl aniline in a manner analogous to Example 1. MH+/Z=280.
Reaction SMILES: [C:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([CH3:13])[N:4]=1)#[N:2].C(C1C=C(CN)C=CN=1)(C)C>>[NH2:2][CH2:1][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([CH3:13])[N:4]=1
Reactant: COC(=O)c1ccc(C#N)nc1C
Agent: CC(C)c1cc(CN)ccn1
Product: COC(=O)c1ccc(CN)nc1C

Procedure:
methyl 6-(aminomethyl)-2-methylnicotinate was synthesized from methyl 6-cyano-2-methylnicotinate following the general procedure as described for 2-isopropyl-4-pyridylmethylamine.
Reaction SMILES: [CH:1]1([C:7](Cl)=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:10][C:11]1([C:27]#[N:28])[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)(Cl)Cl>[Cl:26][C:22]1[CH:21]=[C:20]([S:17]([N:14]2[CH2:13][CH2:12][C:11]([NH:10][C:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[O:8])([C:27]#[N:28])[CH2:16][CH2:15]2)(=[O:18])=[O:19])[CH:25]=[CH:24][CH:23]=1
Reactant: N#CC1(N)CCN(S(=O)(=O)c2cccc(Cl)c2)CC1
Reactant: O=C(Cl)C1CCCCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: N#CC1(NC(=O)C2CCCCC2)CCN(S(=O)(=O)c2cccc(Cl)c2)CC1
Reaction time: 2.5 h

Procedure:
A solution of cyclohexanecarbonyl chloride (118 μL, 0.880 mmol) in chloroform (0.25 mL) was added to a mixed solution of 4-amino-1-(3-chloro-benzenesulfonyl)-piperidine-4-carbonitrile (120 mg, 0.400 mmol) in chloroform (1.25 mL) and a saturated aqueous sodium carbonate solution (1.25 mL), and the mixture was vigorously stirred at room temperature for 16 hours. Cyclohexanecarbonyl chloride (51 μL) was further added and the mixture was stirred for 2.5 hours. The organic layer and the aqueous layer were then separated, and the aqueous layer was further extracted with chloroform. The organic layers were combined, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was washed with n-hexane to give cyclohexanecarboxylic[1-(3-chloro-benzenesulfonyl)-4-cyano-piperidin-4-yl]-amide as a white solid. This was used in the next step without further purification.
Reaction SMILES: [OH:1][S:2]([OH:5])(=O)=[O:3].[CH:6]([C:9]1[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=1[NH2:11])([CH3:8])[CH3:7]>O>[NH2:11][C:10]1[CH:12]=[CH:13][C:14]([S:2]([OH:5])(=[O:3])=[O:1])=[CH:15][C:9]=1[CH:6]([CH3:8])[CH3:7]
Reactant: O=S(=O)(O)O
Reactant: CC(C)c1ccccc1N
Solvent: O
Product: CC(C)c1cc(S(=O)(=O)O)ccc1N
Temperature: 80 °C
Reaction time: 3 h

Procedure:
5.7 ml of H2SO4 are added to 10 ml of water, the mixture is heated to 80° C. and 13.5 g of 2-isopropylaniline are then added. The water is evaporated off by heating under vacuum, and the temperature is then gradually raised over one and a half hours to reach 260° C. After 3 hours with stirring and under vacuum at 260° C., the reaction medium is allowed to return to RT and to atmospheric pressure, and is then heated for 30 minutes in the presence of 15 ml of NaOH and 100 ml of water in order to dissolve the reaction medium. The insoluble matter is filtered off, and the mixture is cooled to 5° C. and then acidified to pH 1 by adding concentrated H2SO4. The precipitate formed is filtered off, washed with 5 ml of cold water and dried to obtain 20 g of the expected product.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1.O>C1COCC1>[N+:22]([C:19]1[CH:20]=[CH:21][C:16]([CH2:15][CH2:14][CH2:13][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[CH:17][CH:18]=1)([O-:24])=[O:23]
Reactant: O=[N+]([O-])c1ccc(CCCBr)cc1
Reactant: c1c[nH]cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: O=[N+]([O-])c1ccc(CCCn2ccnc2)cc1
Temperature: 50 °C
Reaction time: 60 h
Yield: 44.3 %

Procedure:
Imidazole (1.3 g) was dissolved in. THF (15.5 ml), potassium carbonate (5.3 g) was added to the mixture, and a solution of 1-(3-bromopropyl)-4-nitrobenzene (3.1 g) in THF (15.5 ml) was added dropwise to the mixture. The mixture was stirred for 60 hours at 50° C., and cooled to room temperature. The reaction solution was added to water, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by silica gel column chromatography, to give 1-[3-(4-nitrophenyl)propyl]imidazole (1.3 g).