Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C@@H:15]([O:16][C:17](=[O:28])[C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([N+:25]([O-:27])=[O:26])[CH:19]=3)[C:14](=[O:29])[NH:13][C:12]3[CH:30]=[CH:31][CH:32]=[CH:33][C:11]=3[S:10]2)=[CH:5][CH:4]=1.[C:34](=[O:37])([O-:36])[O-].[K+].[K+].Cl.[CH3:41][N:42]([CH2:45][CH2:46]Cl)[CH2:43][CH3:44]>CC(C)=O>[C:17]([OH:28])(=[O:16])[C:34]([OH:36])=[O:37].[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[C@@H:15]([O:16][C:17](=[O:28])[C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([N+:25]([O-:27])=[O:26])[CH:19]=3)[C:14](=[O:29])[N:13]([CH2:44][CH2:43][N:42]([CH3:41])[CH2:45][CH3:46])[C:12]3[CH:30]=[CH:31][CH:32]=[CH:33][C:11]=3[S:10]2)=[CH:7][CH:8]=1
Reactant: CCN(C)CCCl
Reactant: O=C([O-])[O-]
Reactant: COc1ccc([C@@H]2Sc3ccccc3NC(=O)[C@@H]2OC(=O)c2ccc(Cl)c([N+](=O)[O-])c2)cc1
Agent: Cl
Agent: [K+]
Solvent: CC(C)=O
Product: CCN(C)CCN1C(=O)[C@H](OC(=O)c2ccc(Cl)c([N+](=O)[O-])c2)[C@H](c2ccc(OC)cc2)Sc2ccccc21
Product: O=C(O)C(=O)O
Yield: 160.6 %

Procedure:
970 mg of (-)-cis-2-(4-methoxyphenyl)-3-(4-chloro-3-nitrobenzoyloxy)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one are dissolved in 20 ml of acetone, and 690 mg of potassium carbonate and 410 mg of 2-(N-methyl-N-ethylamino)ethyl chloride hydrochloride are added thereto. The mixture is refluxed for 3 hours under stirring. After the reaction, the mixture is evaporated under reduced pressure to remove solvent. Ethyl acetate is added to the residue, and the mixture is washed with water. The ethyl acetate solution is dried and evaporated under reduced pressure to remove solvent. 180 mg of oxalic acid and 10 ml of acetone are added to the residue, and the mixture is heated to make a clear solution. The clear solution is allowed to stand. Crystalline precipitates are collected by filtration and dried, whereby 1.06 g of (+)-cis-2-(4-methoxyphenyl)-3-(4-chloro-3-nitrobenzoyloxy)-5-[2-(N-methyl-N-ethylamino)ethyl]-2,3-dihydro-1,5-benzothiazepin-4(5H)-one oxalate are obtained as colorless needles. Yield: 80%.
Reaction SMILES: [CH2:1]([NH:5][CH2:6][CH2:7][CH2:8]O)[CH:2]([CH3:4])[CH3:3].O=S(Cl)[Cl:12]>C1(C)C=CC=CC=1>[ClH:12].[CH2:1]([NH:5][CH2:6][CH2:7][CH2:8][Cl:12])[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)CNCCCO
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Product: CC(C)CNCCCCl
Product: Cl
Reaction time: 4 h

Procedure:
To a solution of N-isobutyl-3-hydroxypropylamine (1.01 g, 7.70 mmol) in toluene (100 mL) was added SOCl2 (1.37 g, 11.6 mmol, 1.5 equiv.) and the resulting mixture was stirred at room temp. for 4 h. The resulting slurry was concentrated under reduced pressure to afford N-isobutyl-3-chloropropylamine HCl salt: 1H NMR (CDCl3) δ1.12 (s, 9H), 1.28 (t, J=7.0 Hz, 3H), 4.24 (q, J=7.0 Hz, 2H), 4.55 (s, 1H), 5.00 (s, 2H); 13C NMR (CDCl3) δ13.9, 27.8, 38.2, 61.5, 67.1, 67.3, 117.0, 167.1, 180.7; CI-LRMS m/z (rel abundance) 150 ((M+H)+, 100%).
Reaction SMILES: CO[C:3]1[N:11]=[CH:10][N:9]=[C:8]2[C:4]=1[N:5]=[CH:6][N:7]2[CH2:12][O:13][CH2:14][CH2:15][P:16](=[O:23])([O:20]CC)[O:17][CH2:18][CH3:19].[NH3:24]>CO>[N:11]1[C:3]([NH2:24])=[C:4]2[C:8]([N:7]([CH2:12][O:13][CH2:14][CH2:15][P:16](=[O:23])([O-:20])[O:17][CH2:18][CH3:19])[CH:6]=[N:5]2)=[N:9][CH:10]=1.[NH4+:5]
Reactant: N
Reactant: CCOP(=O)(CCOCn1cnc2c(OC)ncnc21)OCC
Solvent: CO
Product: CCOP(=O)([O-])CCOCn1cnc2c(N)ncnc21
Product: [NH4+]
Temperature: 100 °C
Yield: 40 %

Procedure:
To a solution of 11 (3.44 g, 10.0 mmol) in MeOH (40 mL) was added a saturated methanolic NH3 solution (100 mL). The solution was heated in a sealed flask at 100° C. for 30 h. The solvent was evaporated and the residue was crystallized from EtOH to give 12 (1.20 g) in 40% yield: mp 190°-193° C.; TLC Rf 0.37 (AcOEt/MeOH=1:1); UV λmax (EtOH): 260 nm (ε14 000); 1H NMR (DMSO-d6 /D2O): δ1.20-1.56 (m, 5 H, CH3 +CH2 P), 3.40-4.10 (m, 2 H, CH2OP), 4.30 (m, 2 H, CH2O), 5.60 (s, 2 H, OCH2N), 7.80, 8.12 (2 s, 2 H, HC(2) +HC(8)). Anal. (C10 H19N6O4P) C, H, N.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[C:12]([OH:22])[C:13]([C:19]([OH:21])=O)=[CH:14]2.ON1C(=O)CCC1=O.[NH2:31][CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][CH:37]([O:40][CH:41]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH2:36][CH2:35]1>ClCCl>[CH:41]([O:40][CH:37]1[CH2:38][CH2:39][N:34]([CH2:33][CH2:32][NH:31][C:19]([C:13]2[C:12]([OH:22])=[CH:11][C:10]3[C:15](=[CH:16][CH:17]=[CH:18][C:9]=3[O:8][CH2:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[CH:14]=2)=[O:21])[CH2:35][CH2:36]1)([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1
Reactant: NCCN1CCC(OC(c2ccccc2)c2ccccc2)CC1
Reactant: O=C(O)c1cc2cccc(OCc3ccccn3)c2cc1O
Agent: O=C1CCC(=O)N1O
Solvent: ClCCl
Product: O=C(NCCN1CCC(OC(c2ccccc2)c2ccccc2)CC1)c1cc2cccc(OCc3ccccn3)c2cc1O
Temperature: 25 °C
Reaction time: 1 h
Yield: 53.8 %

Procedure:
591 mg (2.0 mM) of 5-(2-pyridylmethoxy)3-hydroxy-2-naphthoic acid was dissolved in 20 ml of dichloromethane. Thereto were added 235 mg (2.0 mM) of N-hydroxysuccinimide and 422 mg (2.0 mM) of dicyclocarbodiimide. The resulting mixture was stirred at room temperature for 1 hour. Thereto was dropwise added a solution of 620 mg (2.0 mM) of 1-(2-aminoethyl)-4-(benzhydryloxy)-piperidine in 20 ml of dichloromethane. Stirring was conducted at room temperature for 2 hours to give rise to a reaction. After the completion of the reaction, extraction with dichloromethane was conducted. The extract was washed with a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution two times, and dried over anhydrous sodium sulfate. The solvent was removed by distillation. The residue was mixed with 20 ml of acetonitrile. The mixture was filtered, and the filtrate was subjected to distillation to remove the solvent. The residue was purified by silica gel chromatography to obtain 632 mg of the title compound at a yield of 67%.
Reaction SMILES: [CH2:1]([N:5]1[C:9]([CH:10]=[O:11])=[CH:8][N:7]=[C:6]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].[BH4-].[Na+]>CO.O>[CH2:1]([N:5]1[C:9]([CH2:10][OH:11])=[CH:8][N:7]=[C:6]1[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1c(C=O)cnc1-c1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCCCn1c(CO)cnc1-c1ccccc1

Procedure:
Aldehyde 102 is dissolved in methanol (150 mL). Sodium borohydride (3 g) is added in portions. After the addition was complete, the reaction is diluted with water and concentrated. The residue is dissolved in ethyl acetate, washed with brine, dried (Na2SO4) and concentrated. The product is purified by flash chromatography on silica gel (5% MeOH/CHCl3) to give 4.17 g of 103 as a cream colored solid. 1H-NMR (400 MHz, CDCl3): δ 0.79 (3H, t, d=7.4), 1.18 (2H, m, d=7.4), 1.60 (2H, m, d=7.6), 4.03 (2H, dd, d=7.6), 4.56 (2H, s), 6.84 (1H, s), 7.39-7.50 (3H, m),7.50-7.53 (2H, m).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:10][CH2:11][S:12]C(=O)C)=[CH:4][CH:3]=1.CN>C(O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:10][CH2:11][SH:12])=[CH:4][CH:3]=1
Reactant: CC(=O)SCCN(Cc1ccc(Cl)nc1)CC(C)C
Agent: CN
Solvent: CCO
Product: CC(C)CN(CCS)Cc1ccc(Cl)nc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 93.3 %

Procedure:
A mixture of 1.23 gram (0.0041 mole) of 1-(2-{[(6-chloro(3-pyridyl))methyl](2-methylpropyl)amino}ethylthio)ethan-1-one (prepared in a manner analogous to Example 1, Step B) and 3.8 grams of a 33% solution of methylamine in ethanol (0.041 mole of methylamine) in 10 mL of ethanol was stirred at ambient temperature one hour. The reaction mixture was concentrated under reduced pressure to a residue. The residue was purified by column chromatography on silica gel, eluting with mixtures of ethyl acetate and hexanes. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.99 gram of 2-{[(6-chloro(3-pyridyl))-methyl](2-methylpropyl)amino}ethane-1-thiol. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[N:8]([CH2:18][C:19]#[CH:20])[N:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10]1.[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1.[CH2:26]=O>Cl[Cu].O1CCOCC1>[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[N:8]([CH2:18][C:19]#[C:20][CH2:26][N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1)[N:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10]1
Reactant: C=O
Reactant: C1CCNC1
Reactant: C#CCN(c1ccncc1F)n1ccc2ccccc21
Agent: Cl[Cu]
Solvent: C1COCCO1
Product: Fc1cnccc1N(CC#CCN1CCCC1)n1ccc2ccccc21
Temperature: 80 °C
Reaction time: 3 h
Yield: 147.2 %

Procedure:
To 100 ml of p-dioxane were added N-(3-fluoro-4-pyridinyl)-N-(2-propynyl)-1H-indol-1-amine (3.0 g), pyrrolidine (1.2 g), paraformaldehyde (4 g) and CuCl (0.3 g) and this mixture was heated to 80° C. and stirred for 3 hours. The mixture was then cooled and filtered, and the filtrate was concentrated to yield an oil (5.8 g). This material was eluted with 5% methanol/DCM on a silica gel column via HPLC. The desired fractions were concentrated to yield an oil which solidified on standing (3.3 g). This material was then eluted with DCM on an alumina column. The desired fractions were concentrated to yield a solid (2.2 g), which was recrystallized from hexanes/ether (2:1) to yield a solid (1.5 g), m.p. 76°-78° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([OH:14])=O)[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17].FC1C(OC(N(C)C)=[N+](C)C)=C(F)C(F)=C(F)C=1F.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.C(OC([N:70]1[CH2:76][CH2:75][CH2:74][NH:73][CH2:72][CH2:71]1)=O)(C)(C)C.FC(F)(F)C(O)=O>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:70]1[CH2:76][CH2:75][CH2:74][NH:73][CH2:72][CH2:71]1)=[O:14])[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17]
Reactant: CC(C)(C)OC(=O)N1CCCNCC1
Reactant: CC(Nc1ncnc2cc(C(=O)O)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1
Agent: CN(C)C(Oc1c(F)c(F)c(F)c(F)c1F)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(Nc1ncnc2cc(C(=O)N3CCCNCC3)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1

Procedure:
Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and 1-tert.-butyloxycarbonyl-[1,4]diazepan in DMSO at ambient temperature and subsequent treatment with trifluoroacetic acid.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:10]=1.[C-:23]#[N:24].[Na+]>CCO.O>[CH2:16]([O:15][C:11]1[CH:10]=[C:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[CH2:2][C:23]#[N:24])[CH:14]=[CH:13][CH:12]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: ClCc1ccccc1-c1cccc(OCc2ccccc2)c1
Reactant: [C-]#N
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: N#CCc1ccccc1-c1cccc(OCc2ccccc2)c1
Reaction time: 48 h

Procedure:
To a stirred solution of 2-chloromethyl-3′-benzyloxybiphenyl from Step A (188 mg, 0.61 mmol) in EtOH (4 mL) was added a solution of NaCN (60 mg, 1.22 mmol) in water (4 mL). The resulting solution was heated to reflux for 12 h, stood at ambient temperature for 48 h, then concentrated under reduced pressure. The residue was partitioned between sat. aq. NaHCO3 (10 mL) and CH2Cl2 (20 mL). The aqueous layer was extracted further with CH2Cl2 (2×10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography, eluting with a gradient of 2-10% EtOAc in hexane to give the titled product.
Reaction SMILES: CO[CH:3]([O:11]C)[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1.[Mg].II.Br[C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1>O1CCCC1.O>[N:20]1[CH:21]=[CH:22][C:17]([C:7]2[CH:6]=[CH:5][C:4]([CH:3]=[O:11])=[CH:9][CH:8]=2)=[CH:18][CH:19]=1
Reactant: Brc1ccncc1
Reactant: COC(OC)c1ccc(Br)cc1
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Solvent: O
Product: O=Cc1ccc(-c2ccncc2)cc1
Temperature: 25 °C
Yield: 63.4 %

Procedure:
A solution of 6.93 g of 4-bromobenzaldehyde dimethyl acetal in 40 ml of tetrahydrofuran was dropwise added to a mixture comprising 0.80 g of magnesium powder, a catalytic amount of iodine and 10 ml of tetrahydrofuran under stirring at a temperature in the bulk of 40° to 50° C. in a nitrogen atmosphere to prepare a Grignard reagent. This Grignard reagent was dropwise added to a solution of 4.46 g of 4-bromopyridine and 0.4 g of bis(1,3-diphenylphosphinopropane)nickel (II) chloride in 100 ml of tetrahydrofuran at a room temperature in a nitrogen atmosphere. The obtained mixture was refluxed for 4 hours and allowed to cool to a room temperature, followed by the addition of water. The obtained mixture was distilled to remove the tetrahydrofuran. Ethyl acetate was added to the residue. The obtained mixture was extracted with dilute hydrochloric acid thrice. The extracts were combined, allowed to stand for a short time, made alkaline with concentrated aqueous ammonia and extracted with chloroform. The extract was dried over anhydrous magnesium sulfate and distilled to remove the solvent. The residue was purified by silica gel column chromatography (solvent: chloroform/methanol) to obtain 3.28 g of the title compound as a pale yellow crystal (yield: 64%).
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][C:20]=1[O:21][CH3:22])[N:17]=[CH:16][N:15]=[C:14]2[N:23]1[CH2:28][CH2:27][CH:26]([C:29](=[O:31])[CH3:30])[CH2:25][CH2:24]1.O>CS(C)=O.CCOCC>[CH3:30][C:29]1([CH:26]2[CH2:27][CH2:28][N:23]([C:14]3[C:13]4[C:18](=[CH:19][C:20]([O:21][CH3:22])=[C:11]([O:10][CH3:9])[CH:12]=4)[N:17]=[CH:16][N:15]=3)[CH2:24][CH2:25]2)[CH2:2][O:31]1
Reactant: C[S+](C)(C)=O
Reactant: COc1cc2ncnc(N3CCC(C(C)=O)CC3)c2cc1OC
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Solvent: CCOCC
Product: COc1cc2ncnc(N3CCC(C4(C)CO4)CC3)c2cc1OC

Procedure:
Trimethylsulphoxonium iodide (2.25 g) was added portionwise to a stirred suspension of sodium hydride (0.5 g of a 50% dispersion in oil) in dimethylsulphoxide (20 cm3) and the mixture was stirred for 1 hour after which time 6,7-dimethoxy-4-[4-(1-oxoethyl)piperid-1-yl]quinazoline (3.15 g) was added in DMSO (10 cm3). After 1 hour the mixture was poured into water (50 cm3), extracted with dichloromethane (3×50 cm3) and the dried extracts (MgSO4) were evaporated to give an oil which was chromatographed on silica (Merck 60.9385) eluting with chloroform to give a viscous oil. Trituration with ether gave 2-methyl-2-[1-(6,7-dimethoxyquinazolin-4-yl)piperid-4-yl]oxirane slightly contaminated with the starting ketone (2.0 g).
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[O:13]=[CH:14][C@H:15]([C@H:17]([C@@H:19]([C@H:21]([CH2:23][OH:24])[OH:22])[OH:20])[OH:18])[OH:16].OCC([C@H]([C@@H]([C@@H](CO)O)O)O)=O.O=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.O=C[C@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O>>[OH:12][CH2:11][C@@H:9]([C@H:7]([C@@H:5]([C@@H:3]([CH2:2][OH:1])[OH:4])[OH:6])[OH:8])[OH:10].[CH2:23]([OH:24])[C@H:21]([C@H:19]([C@@H:17]([C@@H:15]([CH2:14][OH:13])[OH:16])[OH:18])[OH:20])[OH:22]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO
Reactant: O=C[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO
Agent: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: O=C[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
A method for producing L-sugars including L-idose and L-gulose as well as D-fructose from D-glucose. The method comprises epimerizing D-glucose to a mixture of D-glucose and D-mannose, hydrogenating the mixture in a fixed catalyst bed to provide D-sorbitol and D-mannitol, separating the D-mannitol by fractional crystallization, oxydizing separately the D-sorbitol and D-mannitol to provide L-sorbose and D-fructose, respectively; and racemizing the L-sorbose in a weak alkaline solution to provide a mixture of L-sorbose, L-idose and L-gulose, and precipitating the remaining L-sorbose with a dilute lime solution. The unconverted L-sorbose is recovered and recycled.
Reaction SMILES: [C:1]1([S:7]([NH:10][C:11]2[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=2)[C:14]([OH:16])=O)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN([P+](ON1N=NC2C1=CC=CC=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.[OH:57][C:58]1[CH:65]=[CH:64][C:61]([CH2:62][NH2:63])=[CH:60][C:59]=1[O:66][CH3:67]>CN(C)C=O>[C:1]1([S:7]([NH:10][C:11]2[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=2)[C:14]([NH:63][CH2:62][C:61]2[CH:64]=[CH:65][C:58]([OH:57])=[C:59]([O:66][CH3:67])[CH:60]=2)=[O:16])(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(O)c1cccc(NS(=O)(=O)c2ccccc2)c1
Reactant: COc1cc(CN)ccc1O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(CNC(=O)c2cccc(NS(=O)(=O)c3ccccc3)c2)ccc1O
Reaction time: 0.08 h

Procedure:
To 139 mg (0.5 mmol) of 3-(phenylsulfonyl)aminobenzoic acid as prepared in Example 9 in 1 mL of N,N-dimethylformamide was added sequentially 1 mL of 0.5M (0.5 mmol) of Castro's reagent (benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate) in N,N-dimethylformamide and then 500 μL of N,N-diisopropylethylamine. After 5 min, 95 mg (0.5 mmol) of 4-hydroxy-3-methoxybenzylamine HCl was added. After 30 min, the reaction mixture was quenched with 7 mL of 2N HCl, extracted into ethyl acetate (2×2 mL), washed with water (3×4 mL) and then sat. NaHCO3 (1×4 mL). The organic phase was passed through a Waters solid phase extraction column (5 g silica gel) onto which was added Na2SO4 to act a drying agent. Elution with ethyl acetate gave the title compound: NMR (DMSO-d6 ; 300 MHz) δ 10.46 (s, 1H), 8.88 (t, 1H), 8.84 (s, 1H), 7.74-7.81 (m, 3H), 7.50-7.70 (m, 6H), 7.30 (t, 1H) 7.22 (d, 1H), 6.87 (s, 1H), 6.69 (t, 2H), 4.31 (d, 2H), 3.73 ppm (s, 3H). Mass spectrum (MALDI-TOF; gentisic acid matrix) cald. for C27H20N2O5S: 435.1 (M+Na). Found: 435.0.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:21]3[C:22]4=[C:23]5[C:18](=[CH:19][CH:20]=3)[CH:17]=[CH:16][CH:15]=[C:14]5[CH:13]=[CH:12][C:11]4=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[Br:24]N1C(=O)CCC1=O.CN(C)C=O>O>[Br:24][C:15]1[C:14]2[C:23]3=[C:22]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][C:8]([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)=[C:21]4[CH:20]=[CH:19][C:18]3=[CH:17][CH:16]=1
Reactant: Cc1ccc(-c2ccc3ccc4cccc5ccc2c3c45)cc1
Reactant: O=C1CCC(=O)N1Br
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(-c2ccc3ccc4c(Br)ccc5ccc2c3c54)cc1
Temperature: 40 °C
Reaction time: 7 h
Yield: 22.4 %

Procedure:
Next, a mixed solution of 40.0 g of 1-(4-methylphenyl)pyrene, 24.4 g of N-bromosuccinimide and 1.4 L of dimethylformamide was heated with stirring under a nitrogen gas flow at 40° C. for 7 hours. After cooling the solution to room temperature, 1.0 L of water was injected, followed by extraction with 500 ml of dichloromethane. The organic layer was washed twice with 200 ml of water, dried over magnesium sulfate, evaporated and then filtered using Celite. The filtrate was evaporated and the residue was washed twice with 200 ml of ethyl acetate. The precipitated solid was collected by filtration and then vacuum-dried to obtain 11.4 g of 1-bromo-6-(4-methylphenyl)pyrene.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:34])=[C:14]([C:29](OCC)=[O:30])[C:15](=[O:28])[N:16]3[CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][C:22]3=[O:27])=[N:11][CH:10]=2)=[CH:4][CH:3]=1.[NH2:35][CH2:36][CH:37]([OH:40])[CH2:38][CH3:39]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:34])=[C:14]([C:29]([NH:35][CH2:36][CH:37]([OH:40])[CH2:38][CH3:39])=[O:30])[C:15](=[O:28])[N:16]3[CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][C:22]3=[O:27])=[N:11][CH:10]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(CCN2CCCCC2=O)c1=O
Reactant: CCC(O)CN
Product: CCC(O)CNC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(CCN2CCCCC2=O)c1=O

Procedure:
This compound was prepared from ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1-[2-(2-oxo-1-piperidinyl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxylate and 1-amino-2-butanol using methods similar to Example 563 to provide an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 0.83-0.93 (m, 3 H), 1.38-1.45 (m, 2 H), 1.54-1.65 (m, 4 H), 2.04 (t, J=6.00 Hz, 2 H), 3.18-3.30 (m, 3 H), 3.44-3.57 (m, 4 H), 4.16 (s, 2 H), 4.31-4.45 (m, 2 H), 4.95 (d, J=5.26 Hz, 1 H), 7.11-7.18 (m, 2 H), 7.38-7.44 (m, 2 H), 8.20 (s, 1 H), 8.56 (d, J=1.68 Hz, 1 H), 10.42 (t, J=5.58 Hz, 1 H), 17.23 (s, 1 H); ES+ MS: 511 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[O:8][CH:7]=[C:6]([C:13]1[CH:24]=[CH:23][C:16]([O:17][CH2:18][CH2:19][CH2:20][C:21]#[N:22])=[C:15]([O:25][CH2:26][CH2:27][CH2:28][C:29]#[N:30])[CH:14]=1)[C:5]2=O.O.[NH2:33][NH2:34]>>[Cl:1][C:2]1[C:11]([OH:12])=[CH:10][C:9]([OH:8])=[C:4]([C:5]2[C:6]([C:13]3[CH:24]=[CH:23][C:16]([O:17][CH2:18][CH2:19][CH2:20][C:21]#[N:22])=[C:15]([O:25][CH2:26][CH2:27][CH2:28][C:29]#[N:30])[CH:14]=3)=[CH:7][NH:34][N:33]=2)[CH:3]=1
Reactant: N#CCCCOc1ccc(-c2coc3cc(O)c(Cl)cc3c2=O)cc1OCCCC#N
Reactant: NN
Solvent: O
Product: N#CCCCOc1ccc(-c2c[nH]nc2-c2cc(Cl)c(O)cc2O)cc1OCCCC#N
Yield: 90.1 %

Procedure:
This compound was synthesised in the same manner as described above. 4-[4-(6-Chloro-7-hydroxy-4-oxo-4H-chromen-3-yl)-2-(3-cyano-propoxy)-phenoxy]-butyronitrile (0.12 g, 0.27 mmol), Hydrazine hydrate (5 ml). The precipitate formed on quenching was filtered to give 4-[4-[3-(5-Chloro-2,4-dihydroxy-phenyl)-1H-pyrazol-4-yl]-2-(3-cyano-propoxy)-phenoxy]-butyronitrile as a white solid (0.11 g, 90.1%); Rf 0.6 ethyl acetate/hexane (70/30)].
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)[C:10](OC)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH3:24]>CO>[NH2:24][C:10](=[O:11])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1
Reactant: N
Reactant: COC(=O)[C@@H](Cc1c[nH]c2ccccc12)NC(=O)OC(C)(C)C
Solvent: CO
Product: CC(C)(C)OC(=O)N[C@H](Cc1c[nH]c2ccccc12)C(N)=O
Temperature: 85 °C
Reaction time: 24 h

Procedure:
In a reactor under 200 psi of pressure was added (6.2 g, 22 mmol) of methyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propanoate and 120 ml of methanol saturated with NH3. The solution was stirred at about 85° C. for about 24 hours. After cooling, the solution was evaporated and the residue precipitated by the addition of diisopropyl ether. Filtration gave 5.4 g of the title product as a white powder. Melting point: 142-143° C.
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5]([N:8]2[C:12]([NH2:13])=[C:11]([C:14](=O)[NH2:15])[CH:10]=[N:9]2)=[CH:6][CH:7]=1.[CH3:17][NH:18][NH2:19]>CN(C)C=O>[CH3:17][N:18]([C:2]1[N:3]=[N:4][C:5]([N:8]2[C:12]([NH2:13])=[C:11]([C:14]#[N:15])[CH:10]=[N:9]2)=[CH:6][CH:7]=1)[NH2:19]
Reactant: CNN
Reactant: NC(=O)c1cnn(-c2ccc(Cl)nn2)c1N
Solvent: CN(C)C=O
Product: CN(N)c1ccc(-n2ncc(C#N)c2N)nn1

Procedure:
A mixture of 2.2 g. (10 mmoles) of 3-chloro-6-(4-cyano-5-amino-1-pyrazolyl)-pyridazine (prepared according to Example 24), 1.38 g. (30 mmoles) of methylhydrazine and 25 ml. of dimethylformamide is heated at 120°-130° C. for 7.5 hours, and after cooling the mixture is poured onto ice. The separated crystals are filtered, washed with water and triturated with 5 ml. of hot ethanol, filtered and dried. Yield: 2.1 g. (91%); m.p.: 260° C. (with decomposition).