Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH:3]([CH2:11][OH:12])[CH2:2]1.[C:13]1(C)[C:14]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:16]=[CH:17][CH:18]=1.N1C=CC=C[CH:25]=1>>[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH:3]([CH2:11][O:12][S:19]([C:14]2[CH:13]=[CH:18][C:17]([CH3:25])=[CH:16][CH:15]=2)(=[O:20])=[O:21])[CH2:2]1
Reactant: Cc1ccccc1S(=O)(=O)Cl
Reactant: OCC1COc2ccccc2C1
Reactant: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCC2COc3ccccc3C2)cc1
Reaction time: 6 h

Procedure:
Compound 18A (3.6 g) was dissolved in pyridine (11 mL) at RT. Toluene sulfonyl chloride (4.5 g) was added, stirred for 6 h. The reaction mixture was quenched with 2N HCl (500 mL), ether extraction (2×200 mL). The combined ether was washed with water, brine, dried (MgSO4), concentrated, to afford an orange color solid, compound 18B (4.2 g). mp 83-84° C.; MS: 319 (M+1)+. Preparation of Chroman-3-yl-acetonitrile (Compound 18C)
Reaction SMILES: [CH2:1]([CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][C:9]([O:15][CH2:16][C:17]3[CH:26]=[CH:25][C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[N:18]=3)=[CH:10][CH:11]=2)[C:6]1=[O:27])[CH2:2][CH2:3][CH3:4].[BH4-].[Na+].C(Cl)(Cl)[Cl:31]>CO.CCOCC.C(OCC)(=O)C>[ClH:31].[CH2:1]([CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][C:9]([O:15][CH2:16][C:17]3[CH:26]=[CH:25][C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[N:18]=3)=[CH:10][CH:11]=2)[CH:6]1[OH:27])[CH2:2][CH2:3][CH3:4]
Reactant: ClC(Cl)Cl
Reactant: CCCCC1CCc2ccc(OCc3ccc4ccccc4n3)cc2C1=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: CCOCC
Product: CCCCC1CCc2ccc(OCc3ccc4ccccc4n3)cc2C1O
Product: Cl

Procedure:
To a stirring solution of 2-butyl-3,4-dihydro-7-(2-quinolylmethoxy)-1(2H)-naphthalenone (718 mg) in methanol (7 ml) in an ice bath was added dropwise a solution of sodium borohydride (114 mg) in methanol (7 ml). The mixture was stirred for half an hour at the same temperature and then diluted with chloroform (80 ml). The solution was washed with water (80 ml). The aqueous layer was extracted three times with chloroform. The combined organic layers were washed with water, dried and concentrated in vacuo to give an oily residue. The residue was dissolved in ether (200 ml) and thereto N-hydrogen chloride in ethyl acetate (1 ml) was added dropwise with stirring in an ice bath. The precipitates were collected by filtration and washed with ether to yield 2-butyl-7-(2-quinolylmethoxy)-1,2,3,4-tetrahydro-1-naphthol hydrochloride (700 mg). mp: 128°-131° C. IR (Nujol): 3220, 1607, 1598, 1501 cm-1. NMR (CD3OD, δ): 0.80-1.05 (3H, m), 1.10-2.17 (9H, m), 2.60-2.84 (2H, m), 4.30 (0.5H, d, J=7 Hz), 4.58 (0.5H, s), 5.70 (2H, s), 6.94-7.17 (2H, m), 7.25 (1H, d, J=2 Hz), 7.99 (1H, t, J=8 Hz), 8.18 (1H, d, J=8 Hz), 8.20 (1H, t, J=8 Hz), 8.32-8.43 (2H, m), 9.16 (1H, d, J=8 Hz).
Reaction SMILES: [C:1]1([C:7]2[O:8][C:9]3[CH2:10][NH:11][CH2:12][CH2:13][C:14]=3[N:15]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[OH:17][CH:18]([CH2:22][CH3:23])[C:19](O)=[O:20].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(Cl)Cl>[OH:17][CH:18]([CH2:22][CH3:23])[C:19]([N:11]1[CH2:12][CH2:13][C:14]2[N:15]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:8][C:9]=2[CH2:10]1)=[O:20]
Reactant: CCC(O)C(=O)O
Reactant: c1ccc(-c2nc3c(o2)CNCC3)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCC(O)C(=O)N1CCc2nc(-c3ccccc3)oc2C1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
1.14 g (4.80 mmol) 2-phenyl-4,5,6,7-tetrahydro-oxazolo[5,4-c]pyridine×HCl, 500.00 g (4.80 mmol) 2-hydroxybutanoic acid are placed in 10 mL DMF. Then 2.60 mL (18.51 mmol) triethylamine and 2.10 g (5.52 mmol) HATU are added and the mixture is stirred for 30 min at RT. The DMF is eliminated i.V., the residue is added to DCM and extracted 1 time each with 5% potassium hydrogen carbonate solution and 1N HCl. The solvent of the org. phase is eliminated in vacuo and the residue is purified on silica gel. (Eluant: cyclohexane/EA).
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[C:13]([N:20]1[C@@H:24]([CH2:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[CH:23]([CH2:32][CH2:33]O)[O:22][C:21]1([CH3:36])[CH3:35])([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br-:56].[NH+]1C=CC=CC=1>C(Cl)Cl.O>[C:13]([N:20]1[C@@H:24]([CH2:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[CH:23]([CH2:32][CH2:33][Br:56])[O:22][C:21]1([CH3:36])[CH3:35])([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]
Reactant: [Br-]
Reactant: CC(C)(C)OC(=O)N1[C@@H](CC2CCCCC2)C(CCO)OC1(C)C
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1cc[nH+]cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1[C@@H](CC2CCCCC2)C(CCBr)OC1(C)C
Reaction time: 16 h

Procedure:
1.6 ml of diethyl azodicarboxylate are added dropwise, at 20° C. under argon, to 690 mg of 3-Boc-4(S)-cyclohexylmethyl-2,2-dimethyl-5-(2-hydroxyethyl)oxazolidine, 2.6 g of triphenylphosphine and 1.6 g of pyridinium bromide in 15 ml of CH2Cl2. After 16 h at R.T., H2O is added and the mixture is diluted with 100 ml of CH2Cl2. The organic phase is washed twice with saturated NaHCO3 solution and once with saturated NaCl solution. The organic phase is dried with Na2SO4 and concentrated, and the residue is taken up in a little EA and filtered to remove PPh3. Purification on silica gel provides the title compound (eluent: H/EA 15:1).
Reaction SMILES: [CH3:1][CH:2]1[C:14]2[N:13]3[CH:15]=[CH:16][N:17]=[C:12]3[C:11](=[O:18])[NH:10][C:9]=2[C:8]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]1=2.[H-].[Na+].C[Si](C)(C)Cl.Br[CH2:27][CH2:28][CH:29](Cl)[CH3:30].[NH:32]1[CH:36]=[CH:35][N:34]=[CH:33]1>CN(C)C=O>[N:32]1([CH2:27][CH2:28][CH2:29][CH2:30][C:2]2([CH3:1])[C:14]3[N:13]4[CH:15]=[CH:16][N:17]=[C:12]4[C:11](=[O:18])[NH:10][C:9]=3[C:8]3[CH:7]=[CH:6][CH:5]=[CH:4][C:3]2=3)[CH:36]=[CH:35][N:34]=[CH:33]1
Reactant: c1c[nH]cn1
Reactant: CC1c2ccccc2-c2[nH]c(=O)c3nccn3c21
Reactant: CC(Cl)CCBr
Agent: C[Si](C)(C)Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1(CCCCn2ccnc2)c2ccccc2-c2[nH]c(=O)c3nccn3c21

Procedure:
The process is performed as in Example 33 but starting with 0.48 g of 10-methyl-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one, 25 ml of dimethylformamide, 0.33 g of 80% sodium hydride, 0.30 ml of trimethylchlorosilane, 0.25 ml of 1-bromo-3-chlorobutane and 0.15 g of imidazole. After chromatography on a column of silica (20 g), eluting with a mixture of chloroform, methanol and 28% aqueous ammonia (90/7/3 by volume), 0.26 g of 10-[4-(imidazol-1-yl)butyl]-10-methyl-5H,10H-imidazo[1,2-a]indeno-[1,2-e]pyrazin-4-one is obtained in the form of a cream-coloured solid melting at about 160° C. (Analysis, % calculated C: 70.18, H: 5.89, N: 19.48, O: 4.45, % found C: 70.3, H: 6.0, N: 19.6).
Reaction SMILES: O([C:8]1[CH2:13][CH2:12][CH2:11][C:10](=O)[C:9]=1[C:15](=O)[CH:16]=[CH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)C1C=CC=CC=1.[OH2:25].[NH2:26][NH2:27]>CC(O)=O.CCO>[O:25]([C:12]1[CH2:11][CH2:10][C:9]2[C:15]([CH:16]=[CH:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[N:26][NH:27][C:8]=2[CH:13]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: NN
Reactant: O=C(C=Cc1ccccc1)C1=C(Oc2ccccc2)CCCC1=O
Reactant: O
Solvent: CC(=O)O
Solvent: CCO
Product: C(=Cc1n[nH]c2c1CCC(Oc1ccccc1)=C2)c1ccccc1
Temperature: 70 °C
Yield: 72.8 %

Procedure:
To a stirred solution of 3-phenoxy-(3-phenyl-acryloyl)-cyclohex-2-enone (1.13 g, 3.55 mmol) in 20 mL of HOAc/EtOH (1:1) was added hydrazine monohydrate (0.21 mL, 4.3 mmol). The reaction was heated at 70° C. for 3 h, cooled and poured cautiously into saturated Na HCO3 solution and extracted with EtOAc (2×). The combined organic layers were washed with saturated NaCl solution, dried (MgSO4) and concentrated under reduced pressure. The residue was chromatographed on silica gel eluting hexanes/EtOAc (2:1) to give 6-phenoxy-3-styryl-4,5-dihydro-1H-indazole (3) as an off-white solid (406 mg, 36%): 1H NMR (DMSO-d6) δ 2.64 (t, 2H, J=8.0 Hz), 2.95 (t, 2H, J=8.0 Hz), 5.46 (s, 1H), 7.04 (AB, 2H, J=16.8 Hz), 7.15 (d, 2H, J=8.1 Hz), 7.25 (m, 2H), 7.42 (m, 4H), 7.55 (d, 2H, J=7.7 Hz), 12.44 (s, 1H). Anal. Calc. for C2H18N2O.0.2H2O: C, 79.32; H, 5.83; N, 8.81. Found: C, 79.36; H, 5.85; N, 8.84.
Reaction SMILES: [C:1]([CH2:6][NH:7][C:8]1[CH:9]=[C:10]([OH:31])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16](=[O:30])[NH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])([O:3]CC)=[O:2].[OH-].[Na+].Cl>CO.O>[C:1]([CH2:6][NH:7][C:8]1[CH:9]=[C:10]([OH:31])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16](=[O:30])[NH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])([OH:3])=[O:2]
Reactant: CCCCCCCCCCCCNC(=O)COc1ccc(O)cc1NCC(=O)OCC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCCCCCCCCCCCNC(=O)COc1ccc(O)cc1NCC(=O)O
Reaction time: 0.17 h

Procedure:
To a suspension of 40 g of 3-carboethoxymethylamino-4-dodecylcarbamoylmethoxyphenol in 500 ml of methanol was added over 20 minutes a solution of 12 g of sodium hydroxide in 100 ml of water kept at below 20° C., and the mixture was stirred for 10 minutes to obtain a perfect solution. The resulting solution was poured into 2 liters of a 5% hydrochloric acid solution, whereupon pale green crystals were separated. The crystals were recrystallized from a water-methanol mixture to obtain the title compound. The yield was 32 g, and the melting point was 122°-125° C.
Reaction SMILES: [CH2:1]([N:8]1[C:12]([C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=2[NH2:20])=[N:11][N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]1([S:27](Cl)(=[O:29])=[O:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>N1C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([N:8]1[C:12]([C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=2[NH:20][S:27]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:29])=[O:28])=[N:11][N:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cccc(N)c1-c1nnnn1Cc1ccccc1
Reactant: O=S(=O)(Cl)c1ccccc1
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: Cc1cccc(NS(=O)(=O)c2ccccc2)c1-c1nnnn1Cc1ccccc1
Reaction time: 8 h
Yield: 98.7 %

Procedure:
2-(1-Benzyl-1H-tetrazol-5-yl)-3-methylphenylamine (Intermediate 16, 0.15 g) was dissolved in pyridine (5 mL) and benzenesulfonyl chloride (0.07 g, 0.4 mmol) was added. The mixture was stirred overnight, then diluted with ethyl acetate and washed with 1N hydrochloric acid, dried with magnesium sulfate and filtered. The filtrate was evaporated to dryness and the residue was purified by flash chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane. The fractions containing the desired product were combined and evaporated to give the title compound as a white powder (0.16 g).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13][NH2:14].[OH:15][CH2:16][C@@H:17]([NH:25][C:26](=[O:30])[C:27](O)=[O:28])[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13][NH:14][C:27](=[O:28])[C:26]([NH:25][C@@H:17]([CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[CH2:16][OH:15])=[O:30]
Reactant: NCCc1c[nH]c2ccc(Cl)cc12
Reactant: O=C(O)C(=O)N[C@H](CO)Cc1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(NCCc1c[nH]c2ccc(Cl)cc12)C(=O)N[C@H](CO)Cc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 57.6 %

Procedure:
The mixture of 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.256 g; 1.09 mmol), (S)-2-(1-hydroxy-3-phenylpropan-2-ylamino)-2-oxoacetic acid (0.267 g; 1.19 mmol), HATU (0.413 g: 1.09 mmol) and N,N-diisopropylethylamine (0.474 mL; 2.71 mmol) in DMF (5 mL) was stirred at room temperature overnight and concentrated under reduced pressure. The residue was dissolved in dichloromethane, the organic layer was washed with water, and was concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluent 1 to 10% methanol in dichloromethane) to yield 0.251 g (58%) of (S)—N1-(2-(5-chloro-1H-indol-3-yl)ethyl)-N2-(1-hydroxy-3-phenylpropan-2-yl)oxalamide as a white solid.
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([NH:10][C:11]([C@@H:13]1[C@@H:17]([OH:18])[C@@H:16]([OH:19])[C@H:15]([N:20]2[CH:28]=[N:27][C:26]3[C:21]2=[N:22][C:23]([N:44]2[CH2:48][CH2:47][C@@H:46]([NH2:49])[CH2:45]2)=[N:24][C:25]=3[NH:29][CH2:30][CH:31]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:14]1)=[O:12])[CH3:9].C1([O:56][C:57](=O)[NH:58][CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[C:62]([OH:66])[CH:61]=2)C=CC=CC=1>CO>[CH2:8]([NH:10][C:11]([C@@H:13]1[C@@H:17]([OH:18])[C@@H:16]([OH:19])[C@H:15]([N:20]2[CH:28]=[N:27][C:26]3[C:21]2=[N:22][C:23]([N:44]2[CH2:48][CH2:47][C@@H:46]([NH:49][C:57]([NH:58][CH2:59][C:60]4[CH:65]=[CH:64][CH:63]=[C:62]([OH:66])[CH:61]=4)=[O:56])[CH2:45]2)=[N:24][C:25]=3[NH:29][CH2:30][CH:31]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:14]1)=[O:12])[CH3:9]
Reactant: O=C(NCc1cccc(O)c1)Oc1ccccc1
Reactant: CCNC(=O)[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(N4CC[C@@H](N)C4)nc32)[C@H](O)[C@@H]1O
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: CCNC(=O)[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(N4CC[C@@H](NC(=O)NCc5cccc(O)c5)C4)nc32)[C@H](O)[C@@H]1O

Procedure:
(2S,3S,4R,5R)-5-[2-((R)-3-Amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-3,4-dihydroxy-tetrahydro-furan-2-carboxylic acid ethylamide trifluoroacetate (Intermediate E) and (3-Hydroxy-benzyl)-carbamic acid phenyl ester (Intermediate UA) are dissolved in methanol and TEA. The reaction mixture is heated using microwave radiation at 100° C. for 30 minutes in the Personal Chemistry Emrys™ Optimizer microwave reactor. The reaction mixture is concentrated in vacuo and purified by C-18 reverse phase column chromatography eluting with acetonitrile:water (0.1% TFA) (gradient 0-100% acetonitrile) to afford the titled compound.
Reaction SMILES: [CH2:1]([Si:3]([CH2:17][CH3:18])([CH2:15][CH3:16])[O:4][C@@H:5]1[C@H:8]([C:9]2[O:10][CH:11]=[CH:12][CH:13]=2)[NH:7][C:6]1=[O:14])[CH3:2].C(N(C(C)C)CC)(C)C.[CH2:28]([O:32][C:33](Cl)=[O:34])[CH2:29][CH2:30][CH3:31]>ClCCl.CN(C1C=CN=CC=1)C>[CH2:17]([Si:3]([CH2:15][CH3:16])([CH2:1][CH3:2])[O:4][C@@H:5]1[C@H:8]([C:9]2[O:10][CH:11]=[CH:12][CH:13]=2)[N:7]([C:33]([O:32][CH2:28][CH2:29][CH2:30][CH3:31])=[O:34])[C:6]1=[O:14])[CH3:18]
Reactant: CC[Si](CC)(CC)O[C@H]1C(=O)N[C@H]1c1ccco1
Reactant: CCCCOC(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCCCOC(=O)N1C(=O)[C@H](O[Si](CC)(CC)CC)[C@@H]1c1ccco1
Reaction time: 1 h
Yield: 65.6 %

Procedure:
(3R,4R)-3-Triethylsilyloxy-4-(2-furyl)azetidin-2-one (0.58 g, 2.17 mmol) in 30 mL of dichloromethane was stirred with diisopropylethyl amine (0.4 mL, 2.30 mmol) and butylchloroformate (0.3 mL, 2.36 mmol) in addition to a catalytic amount of DMAP. The solution was stirred for 1 h and diluted with dichloromethane and washed with brine, dried over MgSO4 and concentrated. The residue was chromatographed over silica gel (eluted with 3:1 hexane/ethyl acetate) to give 523 mg of product (Y: 65%); IR(KBr) 1820, 1734, 1318, 1018, 734 cm-1 ; 1H-NMR (CDCl3, 300 MHz) δ 7.38 (m, 1H), 6.35 (m, 2H), 5.09 (ABq, J=15.5, 5.6 Hz, 2H), 4.14 (m, 2H), 1.56 (m, 2H), 1.28 (s, 2H), 0.87 (t, J=8.7 Hz, 3H), 0.82 (t, J=7.9, 9H), 0.50 (m, 6H); 13C-NMR (CDCl3, 75.5 Hz) δ 165.4, 149.1, 147.6, 142.9, 110.5, 109.9, 77.7, 66.6, 55.9, 30.5, 18.8, 13.6, 6.3, 4.3; DCIMS M+H calcd for C18H29NO5Si: 368, Found: 368.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[NH2:10][C:11]1[CH:15]=[CH:14][NH:13][N:12]=1.[C:16]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])(=[O:21])[CH2:17][C:18]([CH3:20])=O>>[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]1[C:17]([C:16]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[C:18]([CH3:20])[NH:10][C:11]2=[N:12][NH:13][CH:14]=[C:15]12
Reactant: CC(=O)CC(=O)OC(C)(C)C
Reactant: O=Cc1ccccc1Cl
Reactant: Nc1cc[nH]n1
Product: CC1=C(C(=O)OC(C)(C)C)C(c2ccccc2Cl)c2c[nH]nc2N1

Procedure:
The title compound was prepared from 2-chlorobenzaldehyde, 3-aminopyrazole and t-butyl acetoacetate in the same manner as in Example 1.
Reaction SMILES: N1CCCCC1.C([O:10][C:11]1[C:16]([CH3:17])=[C:15]([C:18]2[O:19][C:20]3[CH:26]=[CH:25][C:24]([CH:27]=O)=[CH:23][C:21]=3[CH:22]=2)[O:14][C:13](=[O:29])[C:12]=1[CH3:30])(=O)C.[S:31]1[CH2:35][C:34](=[O:36])[NH:33][C:32]1=[O:37].[OH-].[Na+]>C1COCC1>[CH3:30][C:12]1[C:13](=[O:29])[O:14][C:15]([C:18]2[O:19][C:20]3[CH:26]=[CH:25][C:24]([CH:27]=[C:35]4[C:34](=[O:36])[NH:33][C:32](=[O:37])[S:31]4)=[CH:23][C:21]=3[CH:22]=2)=[C:16]([CH3:17])[C:11]=1[OH:10]
Reactant: O=C1CSC(=O)N1
Reactant: CC(=O)Oc1c(C)c(-c2cc3cc(C=O)ccc3o2)oc(=O)c1C
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: C1CCNCC1
Product: Cc1c(-c2cc3cc(C=C4SC(=O)NC4=O)ccc3o2)oc(=O)c(C)c1O
Reaction time: 1 h

Procedure:
Piperidine (100 mg) was added to a solution of 4-acetyloxy-3,5-dimethyl-6-(5-formylbenzofuran-2-yl)-2H-pyran-2-one (374 mg) and 1,3-thiazolidine-2,4-dione (135 mg) in THF (50 ml), and the mixture was subjected to heated reflux for 4 hours. After cooling, a 15% sodium hydroxide aqueous solution (10 ml) was added to the reaction solution, and then after stirring for one hour it was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH=5/1) to obtain 3,5-dimethyl-6-(5-((3,5-dioxo-2,4-thiazolidinylidene)methyl)benzofuran-2-yl)-4-hydroxy-2H-pyran-2-one.
Reaction SMILES: Cl.[NH2:2][C@@H:3]([C:6]([OH:8])=O)[CH2:4][OH:5].[CH2:9]([NH2:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CO>[CH2:9]([NH:16][C:6](=[O:8])[CH:3]([NH2:2])[CH2:4][OH:5])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: N[C@H](CO)C(=O)O
Reactant: NCc1ccccc1
Agent: Cl
Solvent: CO
Product: NC(CO)C(=O)NCc1ccccc1

Procedure:
HCl (8.00 g, 219.4 mmol) was passed into MeOH (250 mL), and then D-serine ((R)-5) (20.00 g, 190.3 mmol) was added. The reaction solution was heated at reflux (18 h), then benzylamine (81.6 mL, 761 mmol) was added, and then the reaction mixture was heated for additional 18 h. The solvent was removed under reduced pressure, the insoluble salts were filtered, and the excess benzylamine was removed under high vacuum (Kugelrohr). The residue was dissolved in H2O (100 mL), and the product was extracted with CHCl3 (8×200 mL). The organic layers were combined and dried (Na2SO4), and the solvent was removed under reduced pressure. The residue was triturated with Et2O (150 mL) and filtered to vie 10.0 g (27%) of the product as white solid: mp 74-78° C.; [α]23D (c=1, MeOH)=1.6°.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5]/[C:4](=[C:12]2/[C:13]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[N:14][NH:15][C:16]/2=[O:17])/[CH:3]=1.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([SH:31])=[CH:27][CH:26]=1>>[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([S:31][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[NH:5]/[C:4](=[C:12]3/[C:13]([CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[N:14][NH:15][C:16]/3=[O:17])/[CH:3]=2)=[CH:27][CH:26]=1
Reactant: Nc1ccc(S)cc1
Reactant: O=C1NN=C(C2CCCCC2)/C1=C1\C=C(Cl)c2ccccc2N1
Product: Nc1ccc(SC2=C/C(=C3/C(=O)NN=C3C3CCCCC3)Nc3ccccc32)cc1

Procedure:
The title compound was prepared from (Z)-4-(4-chloroquinolin-2(1H)-ylidene)-3-cyclohexyl-1H-pyrazol-5(4H)-one and 4-aminothiophenol using the procedure described in Example 48. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.08-1.19 (m, 3H) 1.29-1.40 (m, 2H) 1.58-1.65 (m, 4H) 1.67 (d, J=9.60 Hz, 2H) 2.37 (t, J=10.23 Hz, 1H) 6.76 (d, J=8.59 Hz, 2H) 6.90 (s, 1H) 7.33 (d, J=8.34 Hz, 2H) 7.63 (t, J=7.33 Hz, 1H) 7.85-7.93 (m, 2H) 8.16 (d, J=8.34 Hz, 1H); ESI-MS: m/z calc'd for C24H24N4OS 416.54. found m/z 417.1 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([CH:14]=O)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].CCCC(C)C>ClCCl>[C:1]([O:5][C:6](=[O:16])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Nc1ccccc1
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](C=O)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CCCC(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@H](CNc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
Trans-(4-Formyl-cyclohexyl)carbamic acid tert-butyl ester (3.27 g, 14.38 mmol) and aniline (1.98 mL, 15.81 mmol) are dissolved in dichloromethane (60 mL) at room temperature. Sodium triacetoxyborohydride (4.57 g, 21.57 mmol) is added in one portion and the mixture is stirred at room temperature for 2.5 hours. 1N sodium hydroxide solution (20 mL) is added and the mixture is stirred at room temperature for a further 10 minutes. The DCM layer is separated and washed successively with water and saturated brine, dried (MgSO4), filtered and evaporated to give a colourless solid. This is slurried with iso-hexane, filtered and dried to give a colourless solid; [MH+ 305]
Reaction SMILES: O=[C:2]([C:9]1[N:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:12]=[CH:11][CH:10]=1)[CH2:3][C:4]([O:6]CC)=O.[C:20]1([C:26](=[NH:28])[NH2:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C=O)C>[C:20]1([C:26]2[NH:28][C:4](=[O:6])[CH:3]=[C:2]([C:9]3[N:13]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:12]=[CH:11][CH:10]=3)[N:27]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CCOC(=O)CC(=O)c1ccnn1-c1ccccc1
Reactant: N=C(N)c1ccccc1
Solvent: CN(C)C=O
Product: O=c1cc(-c2ccnn2-c2ccccc2)nc(-c2ccccc2)[nH]1
Yield: 27.5 %

Procedure:
To a solution of ethyl 3-oxo-3-(1-phenyl-1H-pyrazol-5-yl)propanoate (300 mg) in DMF (10.0 mL) was added benzenecarboximidamide (139 mg) at room temperature. The reaction mixture was heated using a microwave reactor at 140° C. for 30 min. The reaction mixture was extracted with dichloromethane. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane/methanol) to give the title compound (100 mg).
Reaction SMILES: [C:1]([C:3]1[C:7]([CH:8]([OH:18])[C:9]#[C:10][CH:11](OCC)OCC)=[CH:6][N:5]([C:19]2[C:24]([Cl:25])=[CH:23][C:22]([C:26]([F:29])([F:28])[F:27])=[CH:21][C:20]=2[Cl:30])[N:4]=1)#[N:2].[BrH:31].O.CCOCC>O1CCOCC1>[Br:31][C:9]1[CH:10]=[CH:11][O:18][C:8]=1[C:7]1[C:3]([C:1]#[N:2])=[N:4][N:5]([C:19]2[C:24]([Cl:25])=[CH:23][C:22]([C:26]([F:27])([F:28])[F:29])=[CH:21][C:20]=2[Cl:30])[CH:6]=1
Reactant: CCOC(C#CC(O)c1cn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)nc1C#N)OCC
Reactant: Br
Solvent: C1COCCO1
Solvent: O
Solvent: CCOCC
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)cc1-c1occc1Br

Procedure:
To a stirred solution of 3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,4-diethoxy-1-hydroxybut-2-ynyl)pyrazole (0.04 g) in dioxane (1 ml) was added dropwise at room temperature hydrobromic acid (0.04 g). After 30 minutes the reaction mixture was poured into water (10 ml) and ether (10 ml). The organic layer was separated, dried (MgSO4) and evaporated. Recrystallisation from ether/hexane gave the title compound as a pale brown solid, m.p. 99-101° C.