Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:2].C([O-])([O-])=O.[Na+].[Na+].[O:21]=[C:22]1[N:30]([CH2:31][CH2:32][CH3:33])[C:29]2[N:28]=[C:27]([C:34]34[CH2:41][CH2:40][C:37]([CH2:42][CH2:43][C:44]([NH2:46])=O)([CH2:38][CH2:39]3)[CH2:36][CH2:35]4)[NH:26][C:25]=2[C:24](=[O:47])[N:23]1[CH2:48][CH2:49][CH3:50]>C1COCC1>[O:21]=[C:22]1[N:30]([CH2:31][CH2:32][CH3:33])[C:29]2[N:28]=[C:27]([C:34]34[CH2:41][CH2:40][C:37]([CH2:42][CH2:43][C:44]([NH2:46])=[S:2])([CH2:38][CH2:39]3)[CH2:36][CH2:35]4)[NH:26][C:25]=2[C:24](=[O:47])[N:23]1[CH2:48][CH2:49][CH3:50]
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: CCCn1c(=O)c2[nH]c(C34CCC(CCC(N)=O)(CC3)CC4)nc2n(CCC)c1=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCn1c(=O)c2[nH]c(C34CCC(CCC(N)=S)(CC3)CC4)nc2n(CCC)c1=O
Reaction time: 0.33 h
Yield: 56.6 %

Procedure:
A suspension of P4S10 (23 mg, 53 μmol) and Na2CO3 (4 mg, 53 μmol) in THF (4 ml) was stirred vigorously for 20 min and 3-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo-[2.2.2]oct-1-yl]-propionamide (20 mg, 45 μmol) was added. The resulting pale yellow solution was stirred at rt for 1 h, evaporated to dryness and dried in vacuo overnight. The crude material was purified by radial chromatography (1 mm plate) using 2-5% MeOH in CH2Cl2 as eluent to afford a white solid (11 mg, 55%). MS: 432 (MH+).
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[C:10]([C:16]([NH2:18])=O)[NH:11]2.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[Br:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[C:10]([C:16]#[N:18])[NH:11]2
Reactant: NC(=O)c1cc2c(Br)cccc2[nH]1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Product: N#Cc1cc2c(Br)cccc2[nH]1
Yield: 82.3 %

Procedure:
Phosphorous oxychloride (1.9 mL, 20 mmol) was added to a suspension of 4-bromo-1H-indole-2-carboxylic acid amide (1.32 g, 5.5 mmol.) in toluene (10 mL) and the mixture was stirred at reflux for 45 min. On cooling, the mixture was poured into an aqueous Na2CO3 solution (sat., 50 mL) and the mixture stirred until effervescence had subsided. The layers were separated, the aqueous phase extracted with EtOAc and the combined organic layers dried (MgSO4) and evaporated to dryness. The crude material was purified by column chromatography to afford the title compound as a solid (1.00 g, 82%).
Reaction SMILES: [CH:1]1([O:6][C:7](=[O:23])[C@@H:8]([NH:15]C(OC(C)(C)C)=O)[CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH2:5][CH2:4][CH2:3][CH2:2]1>C(O)(C(F)(F)F)=O.C(Cl)Cl.C(Cl)Cl>[CH:1]1([O:6][C:7](=[O:23])[C@@H:8]([NH2:15])[CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(C)(C)OC(=O)N[C@H](C(=O)OC1CCCC1)C1CCCCC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N[C@H](C(=O)OC1CCCC1)C1CCCCC1
Reaction time: 1.5 h
Yield: 96.2 %

Procedure:
(S)-tert-butoxycarbonylamino-cyclohexyl-acetic acid cyclopentyl ester (1.17 g, 3.60 mmol) was dissolved in a TFA/DCM mixture (1:1, 10 ml) at 0° C. The solution was stirred for 90 minutes, the solvent removed in vacuo. The residue was azetroped with a DCM/heptane mixture (2×) to give a gum. The gum was redissolved in DCM (10 ml) and washed with saturated aqueous NaHCO3 solution (3×10 ml), dried (MgSO4) and filtered. The solvent of the filtrate was removed in vacuo to give the product as an oil (0.780 g, 78% yield). 1H NMR (300 MHz, CDCl3), δ: 1.00-1.40 (10H, m, CH×10), 1.50-2.00 (8H, m, CH×8), 3.25 (1H, d, CH, J=7.2 Hz), 5.20 (1H, m, CH).
Reaction SMILES: [CH2:1]([CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][NH:11]1)/[CH:2]=[CH:3]/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH:16]1([C:19](Cl)=[O:20])[CH2:18][CH2:17]1>>[CH2:1]([CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][N:11]1[C:19]([CH:16]1[CH2:18][CH2:17]1)=[O:20])/[CH:2]=[CH:3]/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: C(=C/c1ccccc1)\CC1CCCCN1
Reactant: O=C(Cl)C1CC1
Product: O=C(C1CC1)N1CCCCC1C/C=C/c1ccccc1

Procedure:
Stage a) The method is the same as that of Example 1.1, Stage a), the initial reactants being (E)-2-(cinnamyl)piperidine (Preparation 2A, Stage b) and cyclopropanecarboxylic acid chloride, yielding (E)-2-cinnamyl-1-cyclopropanecarbonylpiperidine (formula II; Ar=C6H5, m=1, n=2, R=cyclopropyl). Yield: 95%.
Reaction SMILES: F[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][N:13]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH:15]=3)[N:10](C3CCCCO3)[N:9]=2)[CH:5]=[CH:4][CH:3]=1.[CH2:29]([NH2:32])[CH2:30][NH2:31]>O>[N:19]1[CH:20]=[CH:21][CH:22]=[C:17]([C:14]2[CH:15]=[C:16]3[C:8]([C:6]4[N:7]=[C:2]([NH:31][CH2:30][CH2:29][NH2:32])[CH:3]=[CH:4][CH:5]=4)=[N:9][NH:10][C:11]3=[CH:12][N:13]=2)[CH:18]=1
Reactant: NCCN
Reactant: Fc1cccc(-c2nn(C3CCCCO3)c3cnc(-c4cccnc4)cc23)n1
Solvent: O
Product: NCCNc1cccc(-c2n[nH]c3cnc(-c4cccnc4)cc23)n1
Temperature: 160 °C

Procedure:
A mixture of 56.3 mg (0.150 mmol) of 3-(6-fluoropyridin-2-yl)-5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine and 1.0 ml (15.0 mmol) of 1,2-ethylenediamine was heated at 160° C. for 30 min. The mixture was mixed with water and extracted with ethyl acetate. The organic extracts were washed with water 3 times, brine, dried over MgSO4 and concentrated. The residue was heated in a mixture of 4 M of hydrogen chloride in 6 ml of dioxane and 2 ml of conc. hydrochloric acid at 60° C. for 18 hours. The mixture was concentrated in high vacuum and triturated with ethyl ether. The solid material was filtered out and washed with ethyl ether to give 143. Yield 37.5 mg (56%) over two steps. ESI MS m/z 332.1 (M+1). 1H NMR (400 MHz, DMSO): 14.27 (s, 1H), 9.57 (s, 1H), 9.30 (s, 1H), 9.19 (d, J=8.0 Hz, 1H), 9.11 (s, 1H), 8.90 (d, J=4.8 Hz, 1H), 8.23 (s, 3H), 8.11 (dd, J=7.9, 5.6 Hz, 1H), 7.68 (d, J=7.5 Hz, 1H), 7.53 (d, J=7.2 Hz, 1H), 6.71 (d, J=7.3 Hz, 1H), 3.75 (t, J=6.0 Hz, 2H), 3.17 (dd, J=11.4, 5.7 Hz, 2H)
Reaction SMILES: [Na].[CH3:2][O:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([CH2:14][S:15]([C:17]2[NH:21][C:20]3[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=3[N:18]=2)=[O:16])[C:9]=1[CH3:26].CCN(CC)CC.[C:34]1([CH3:62])[CH:39]=[CH:38][C:37]([S:40]([CH2:43][CH2:44][O:45][C:46](=[O:61])[CH2:47][O:48][C:49]2[CH:54]=[C:53]([CH3:55])[C:52]([S:56](Cl)(=[O:58])=[O:57])=[C:51]([CH3:60])[CH:50]=2)(=[O:42])=[O:41])=[CH:36][CH:35]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:34]1([CH3:62])[CH:39]=[CH:38][C:37]([S:40]([CH2:43][CH2:44][O:45][C:46](=[O:61])[CH2:47][O:48][C:49]2[CH:50]=[C:51]([CH3:60])[C:52]([S:56]([N:21]3[C:20]4[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=4[N:18]=[C:17]3[S:15]([CH2:14][C:10]3[C:9]([CH3:26])=[C:8]([O:7][CH2:6][CH2:5][CH2:4][O:3][CH3:2])[CH:13]=[CH:12][N:11]=3)=[O:16])(=[O:57])=[O:58])=[C:53]([CH3:55])[CH:54]=2)(=[O:41])=[O:42])=[CH:36][CH:35]=1
Reactant: COCCCOc1ccnc(CS(=O)c2nc3ccccc3[nH]2)c1C
Reactant: Cc1ccc(S(=O)(=O)CCOC(=O)COc2cc(C)c(S(=O)(=O)Cl)c(C)c2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Agent: [Na]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COCCCOc1ccnc(CS(=O)c2nc3ccccc3n2S(=O)(=O)c2c(C)cc(OCC(=O)OCCS(=O)(=O)c3ccc(C)cc3)cc2C)c1C
Temperature: 25 °C
Reaction time: 3 h
Yield: 82.8 %

Procedure:
To a heterogeneous solution of 2-[4-(3-methoxy-propoxy)-3-methyl-pyridin-2-yl-methanesulfinyl]-1H-benzimidazole sodium salt (RABEPRAZOLE sodium salt, 1.0 g, 2.62 mmol) and 5 mL of Et3N in 20 mL of CH2Cl2 was added the chlorosulfonyl ester (Intermediate 13, 1.57 g, 3.41 mmol, 1.3 eq). About 1 g of solid NaHCO3 was added after the chlorosulfonyl ester has dissolved completely in the reaction mixture. The mixture was stirred at room temperature for 3 h. Thereafter the solvent was removed by evaporation and the residual oil was purified by column chromatography (silica gel, CH2Cl2 to 1% MeOH in CH2Cl2) to give 1.7 g (77%) of 3,5-dimethyl-4-{2-[4-(3-methoxy-propoxy)-3-methyl-pyridin-2-yl-methanesulfinyl]-benzimidazole-1-sulfonyl}phenoxyacetic acid 2-(toluene-4-sulfonyl)ethyl ester (Intermediate 58) as a white foam.
Reaction SMILES: [OH:1][C:2]1[N:7]=[C:6]2[C:8]([CH3:12])(C)[CH2:9][CH2:10][C:5]2=[CH:4][C:3]=1[C:13]([OH:15])=[O:14].S(=O)(=O)(O)O.[CH2:21](O)[CH3:22]>>[OH:1][C:2]1[C:3]([C:13]([O:15][CH2:21][CH3:22])=[O:14])=[CH:4][C:5]2[CH2:10][CH2:9][CH2:8][CH2:12][C:6]=2[N:7]=1
Reactant: CC1(C)CCc2cc(C(=O)O)c(O)nc21
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1cc2c(nc1O)CCCC2

Procedure:
2-Hydroxy-7,7-dimethyl-6,7-dihydro-5H-cyclopenta[b]pyridine-3-carboxylic acid (11.0 g) was dissolved in ethanol (100 ml), sulfuric acid (3.4 ml) was added and the mixture was stirred with heating to reflux for 12 hr. The reaction mixture was concentrated under reduced pressure to a half volume, the residue was basified with 8 M aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The extract was washed successively with 1 M aqueous sodium hydroxide solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and the fraction eluted with ethyl acetate-hexane (50:50-85:15) was concentrated under reduced pressure to give the object compound (3.45 g).
Reaction SMILES: [CH:1]1([CH2:4][N:5]([CH2:12][CH2:13][CH3:14])[C:6](=[O:11])[CH2:7][C:8](=[O:10])[CH3:9])[CH2:3][CH2:2]1.S(Cl)([Cl:18])(=O)=O.C(Cl)Cl>C(Cl)(Cl)Cl>[Cl:18][CH:7]([C:8](=[O:10])[CH3:9])[C:6]([N:5]([CH2:4][CH:1]1[CH2:2][CH2:3]1)[CH2:12][CH2:13][CH3:14])=[O:11]
Reactant: CCCN(CC1CC1)C(=O)CC(C)=O
Reactant: O=S(=O)(Cl)Cl
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: CCCN(CC1CC1)C(=O)C(Cl)C(C)=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A stirred solution of N-cyclopropylmethyl-N-propyl-3-oxo-butanamide (scheme 2: (H)) (900 mg, 4.57 mmoles) in chloroform (30 mL) at 0° C. was treated with sulfuryl chloride (1M in methylene chloride, 5.48 mL, 5.48 mmoles). The mixture was stirred at room temperature for 30 minutes and then poured into methylene chloride and washed with 5% sodium bicarbonate solution, brine, and dried over Na2SO4. The solution was concentrated in vacuo and the crude product used without further purification.
Reaction SMILES: [O:1]1[CH:8]2[CH:2]1[CH2:3][CH2:4][N:5]([C:13](=[O:30])[C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:29])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])=[CH:16][CH:15]=1)[C:6]1[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=12.Cl.[CH3:32][NH:33][CH3:34].C(N(CC)CC)C>CO>[CH3:32][N:33]([CH3:34])[C@@H:8]1[C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]([C:13](=[O:30])[C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:21](=[O:29])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])=[CH:18][CH:19]=2)[CH2:4][CH2:3][C@H:2]1[OH:1]
Reactant: O=C(Nc1ccc(C(=O)N2CCC3OC3c3ccccc32)cc1)c1ccccc1Cl
Reactant: CNC
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Product: CN(C)[C@@H]1c2ccccc2N(C(=O)c2ccc(NC(=O)c3ccccc3Cl)cc2)CC[C@H]1O
Yield: 68.6 %

Procedure:
A mixture of 4,5-epoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.5 g), dimethylamine hydrochloride (2.6 g), triethylamine (4.5 g) and methanol (15 ml) is refluxed for 19 hours. After completion of the reaction, the solvent is distilled off and the resulting residue is dissolved in dichloromethane. The mixture is washed successively with water and saturated saline solution. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (eluent; dichloromethane:methanol=50:1), and recrystallized from ethanol/diethyl ether to give trans-5-dimethylamino-4-hydroxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.38 g) as colorless needles, m.p. 180°-182° C.
Reaction SMILES: Cl[C:2]1[C:14]2[C:13](=[O:15])[C:12]3[CH:11]=[CH:10][N:9]=[CH:8][C:7]=3[C:6]=2[C:5]2[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:4]=2[N:3]=1.[CH3:22][N:23]([CH3:27])[CH2:24][CH2:25][NH2:26]>>[CH3:22][N:23]([CH3:27])[CH2:24][CH2:25][NH:26][C:2]1[C:14]2[C:13](=[O:15])[C:12]3[CH:11]=[CH:10][N:9]=[CH:8][C:7]=3[C:6]=2[C:5]2[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:4]=2[N:3]=1
Reactant: COc1ccc2c3c(c(Cl)nc2c1)C(=O)c1ccncc1-3
Reactant: CN(C)CCN
Product: COc1ccc2c3c(c(NCCN(C)C)nc2c1)C(=O)c1ccncc1-3
Temperature: 55 °C
Reaction time: 4 h

Procedure:
6-Chloro-3-methoxy-5,10-diaza-benzo[c]fluoren-7-one (Example 1c-1) (120 mg) was suspended in N,N-dimethylethylenediamine (50 ml) and the mixture was stirred at 55° C. for four hours under Ar. N,N-dimethylethylenediamine was evaporated and the residue was dissolved in dichloromethane. The solution was washed with water and dried over anhydrous sodium sulfate. Dichloromethane was evaporated to dryness. The residue was purified by silica gel column chromatography developed by dichloromethane-methanol-ammonia water (28%)=400:20:1 and dichloromethane-methanol-ammonia water (25%)=300:20:1. The desired product was obtained as a reddish powder. ESI−MS: m/z 349 (MH+); 1H-NMR (CDCl3): δ2.41 (6H, s), 2.72 (2H, t, J=6 Hz), 3.82 (2H, q-like, J=ca 6 Hz), 3.97 (3H, s), 7.00 (1H, dd, J=9 Hz, 2.5 Hz), 7.07 (1H, d, J=2.5 Hz), 7.34 (1H, brt, J=ca 5 Hz), 7.55 (1H, dd, J=4.5 Hz, 1 Hz), 8.05 (1H, d, J=9 Hz), 8.81 (1H, d, 4.5 Hz), 9.27 (1H, d, J=1 Hz).
Reaction SMILES: C([O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]1[C:22]([CH3:24])([CH3:23])[CH2:21][CH2:20][C:19](=[O:25])[C:18]=1[CH3:26])(=O)C.C([O-])([O-])=O.[K+].[K+].Cl>CO.O>[OH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]1[C:22]([CH3:23])([CH3:24])[CH2:21][CH2:20][C:19](=[O:25])[C:18]=1[CH3:26]
Reactant: CC(=O)OCCCCCCCCCCCCC1=C(C)C(=O)CCC1(C)C
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: CC1=C(CCCCCCCCCCCCO)C(C)(C)CCC1=O
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 81 %

Procedure:
To a solution of 3-(12-acetoxydodecyl)-2,4,4-trimethyl-2-cyclohexene-1-one (132 mg, 0.36 mmol, 1 eq.) in dry methanol (8 ml) was added water (3 drops) and K2CO3 (74 mg, 0.54 mmol, 1.5 eq.). After stirring at room temperature for 2.5 hours the solution was neutralized at pH 7 with HCl 5%, extracted with ether, dried with MgSO4 and concentrated in vacuo. The residue was purified by chromatography over silica gel, eluting with hexane-AcOEt (8-2 to 7-3) to give 3-(12-hydroxydodecy)-2,4,4-trimethyl-2-cyclohexen-1-one as a colorless oil (94 mg, 81%).
Reaction SMILES: C([O:5][C:6]([NH:8][CH:9]([CH:22]1[C:34]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:28]2[C:23]1=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:10]([O:12][CH2:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH3:21])[CH:15]=1)=[O:11])=O)(C)(C)C.F[C:36](F)(F)C(O)=O>>[C:6]([NH:8][CH:9]([CH:22]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:28]=2[C:29]2[C:34]1=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:10]([O:12][CH2:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH3:21])[CH:15]=1)=[O:11])(=[O:5])[CH3:36]
Reactant: Cc1cc(C)cc(COC(=O)C(NC(=O)OC(C)(C)C)C2c3ccccc3-c3ccccc32)c1
Reactant: O=C(O)C(F)(F)F
Product: CC(=O)NC(C(=O)OCc1cc(C)cc(C)c1)C1c2ccccc2-c2ccccc21

Procedure:
3,5-Dimethylbenzyl N-t-butoxycarbonyl-2-(9-fluorenyl)glycinate (Example 9d, 0.5g) was dissolved in trifluoroacetic acid (10ml) for 40 minutes then evaporated in vacuo. To a solution of the residue in pyridine (10ml) was added acetic anhydride (1ml) for 16h. The solvent was removed in vacuo and the residue crystallised from diethyl ether/petroleum ether bp 60°-80° C. to give the title compound mp 162°-164° C. Found: C, 78.19; H,. 6.26; N, 3.45. C26H25NO3 requires C,. 78.17; H, 6.30; N, 3.50%. m/z (CI+)=400 (M+H), (CI-)=398 (M-H).
Reaction SMILES: C1(S([CH2:10][C:11]2[N:15]=[C:14]([C:16]3[O:17][CH:18]=[CH:19][CH:20]=3)[NH:13][N:12]=2)(=O)=O)C=CC=CC=1.[F:21][C:22]1[CH:27]=[C:26]([CH:28]=[CH:29][C:30]#[N:31])[CH:25]=[CH:24][N:23]=1>>[F:21][C:22]1[CH:27]=[C:26]([C:28]2[CH:29]=[C:30]([NH2:31])[N:12]3[N:13]=[C:14]([C:16]4[O:17][CH:18]=[CH:19][CH:20]=4)[N:15]=[C:11]3[CH:10]=2)[CH:25]=[CH:24][N:23]=1
Reactant: O=S(=O)(Cc1n[nH]c(-c2ccco2)n1)c1ccccc1
Reactant: N#CC=Cc1ccnc(F)c1
Product: Nc1cc(-c2ccnc(F)c2)cc2nc(-c3ccco3)nn12

Procedure:
The title compound, MS m/e (%): 296 (M+H+, 100), was prepared in accordance with the general method of example 1 from 3-benzenesulfonylmethyl-5-furan-2-yl-1H-[1,2,4]triazole and 3-(2-fluoro-pyridin-4-yl)-acrylonitrile.
Reaction SMILES: [CH2:1]([O:4][CH2:5][CH2:6][S:7][C:8]1[N:12]=[CH:11][NH:10][N:9]=1)[CH:2]=[CH2:3].C(N(CC)CC)C.[CH2:20]([N:22]([CH2:26][CH3:27])[C:23](Cl)=[O:24])[CH3:21]>O1CCCC1>[CH2:20]([N:22]([CH2:26][CH3:27])[C:23]([N:10]1[CH:11]=[N:12][C:8]([S:7][CH2:6][CH2:5][O:4][CH2:1][CH:2]=[CH2:3])=[N:9]1)=[O:24])[CH3:21]
Reactant: CCN(CC)C(=O)Cl
Reactant: C=CCOCCSc1nc[nH]n1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C=CCOCCSc1ncn(C(=O)N(CC)CC)n1

Procedure:
A solution of 7.4 g. 3-(2-allyloxyethylthio)-1,2,4-triazole, 8ml. triethylamine 6.0 g. diethylcarbamoyl chloride in 40 ml. of tetrahydrofuran was heated under reflux for 15 hours. The cooled reaction mixture was filtered to remove triethylamine hydrochloride and the filtrate was evaporated under vacuum to remove the solvent. Further precipitation of amine hydrochloride was filtered off. The filtrate was dissolved in 50 ml. methylene chloride and washed with ice-cold N/10 sodium hydroxide, with N/10 hydrochloric acid and finally with ice-cold water. The solvent was removed by vacuum distillation to give a liquid product, 1-diethylcarbamoyl-3-(2-allyloxyethylthio)-1,2,4-triazole, b.p. 148° - 153°C./0.05 mm. GLC assay showed that the 1-isomer was present to the extent of 98.33%. Elemental analysis was satisfactory.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH2:21][CH2:22][O:23][NH2:24].[O:25]=[C:26]([CH3:30])[C:27](O)=[O:28]>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH2:21][CH2:22][O:23][N:24]=[C:27]([OH:28])[C:26](=[O:25])[CH3:30]
Reactant: CC(=O)C(=O)O
Reactant: CSc1ccc(/C=C2/C(C)=C(CCON)c3cc(F)ccc32)cc1
Product: CSc1ccc(/C=C2/C(C)=C(CCON=C(O)C(C)=O)c3cc(F)ccc32)cc1

Procedure:
The title compound is prepared by reaction of O-2-[Z-5-fluoro-2-methyl-1-(4-methylthiophenyl)methylene-1H-inden-3-yl]ethyl hydroxylamine with 2-oxopropionic acid by the method of Example 1.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:10]([CH2:11][CH3:12])=[N:9][N:8]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:7]=1)=O)C.S([O-])([O-])(=O)=O.[Na+].[Na+]>CCOCC.C1COCC1>[CH2:11]([C:10]1[C:6]([CH2:4][OH:3])=[N:7][N:8]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:9]=1)[CH3:12]
Reactant: CCOC(=O)c1nn(-c2ccccc2)nc1CC
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCc1nn(-c2ccccc2)nc1CO
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.2 %

Procedure:
11.55 g of ethyl-5-ethyl-2-phenyl-1,2,3-triazole-4-carboxylate dissolved in a mixed solvent of 150 ml of ether and 30 ml of THF was added dropwise at 3-8° C. to LiAIH4 suspended in 100 ml of ether. After stirring overnight at room temperature, a small amount of saturated sodium sulfate solution was added thereto. Insoluble materials were filtered off, and the filtrate was dried over anhydrous sodium sulfate. The solvent was distilled off to obtain 9.40 g of the aimed compound.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:16]([O:18][CH:19]1[CH2:24][CH2:23][CH:22]([C:25]([O:27]CC2C=CC(OC)=CC=2)=[O:26])[CH2:21][CH2:20]1)=[O:17])[CH:13]([CH3:15])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:16]([O:18][CH:19]1[CH2:24][CH2:23][CH:22]([C:25]([OH:27])=[O:26])[CH2:21][CH2:20]1)=[O:17])[CH:13]([CH3:15])[CH3:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(COC(=O)C2CCC(OC(=O)[C@@H](NC(=O)OCc3ccccc3)C(C)C)CC2)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)OC1CCC(C(=O)O)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 4-methoxybenzyl 4-(N-benzyloxycarbonyl-L-valyloxy)-cyclohexanoate (12 g, 24.1 mmole) in dichloromethane (100 ml) was added trifluoroacetic acid (20 ml) and the mixture was stirred for 3 hours at room temperature. The solution was evaporated under reduced pressure and coevaporated two times with toluene. The residue was stirred 1 hour with about 100 ml ethanol and the white solid was filtered (byproduct). The solution was evaporated under reduced pressure and the product was isolated by silica gel column chromatography with toluene/acetone. Yield: 6.8 g=74%. The product can be activated and esterified directly to a drug or firer modified as described below.
Reaction SMILES: Cl[C:2]1[C:7]2[CH2:8][C:9]3([CH:15]4[CH2:16][CH2:17][N:12]([CH2:13][CH2:14]4)[CH2:11]3)[O:10][C:6]=2[CH:5]=[CH:4][N:3]=1>CO.[Pd]>[O:10]1[C:6]2[CH:5]=[CH:4][N:3]=[CH:2][C:7]=2[CH2:8][C:9]21[CH:15]1[CH2:14][CH2:13][N:12]([CH2:17][CH2:16]1)[CH2:11]2
Reactant: Clc1nccc2c1CC1(CN3CCC1CC3)O2
Agent: [Pd]
Solvent: CO
Product: c1cc2c(cn1)CC1(CN3CCC1CC3)O2
Reaction time: 2.5 h
Yield: 10.4 %

Procedure:
The 4′-chlorospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[3,2-c]pyridine] (125 mg or 5.0 mmol) from Example 33 was dissolved in 50 mL of anhydrous methanol, and 25 mg of 10% palladium on carbon was added. The bottle was placed on the Parr apparatus under hydrogen atmosphere and shaken for 2.5 hours. The Pd/C was removed by filtration and washed with methanol. The solvent was removed in vacuo and the residue was taken up in chloroform and methanol and transferred to a vial. The solvent was removed in vacuo and chased with two portions of ether. After drying with high vacuum obtained 112 mg of off-white powder (104% with residual solvent.) Electrospray MS 217 [MH]+
Reaction SMILES: Br[CH2:2][C:3](OC)([CH3:6])[CH2:4][OH:5].[Na].[CH2:10]([SH:28])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27].CO>C(O)C>[CH2:6]=[C:3]([CH2:2][S:28][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:4][OH:5]
Reactant: CCCCCCCCCCCCCCCCCCS
Reactant: COC(C)(CO)CBr
Agent: [Na]
Solvent: CO
Solvent: CCO
Product: C=C(CO)CSCCCCCCCCCCCCCCCCCC

Procedure:
3-Bromo-2-methoxy-2-methylpropan-1-ol is reacted with the sodium salt of octadecanethiol in ethanol. The 2-methylene-3-octadecylthiopropan-1-ol (wax-like substance) is thereby obtained with the splitting off of methanol.
Reaction SMILES: [N:1]([CH2:4][C@@H:5]([NH2:15])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[Cl:14])=[N+:2]=[N-:3].[OH:16][C@H:17]1[C:21]2[N:22]=[CH:23][N:24]=[C:25]([C:26]3[S:30][C:29]([C:31](O)=[O:32])=[CH:28][CH:27]=3)[C:20]=2[C@H:19]([CH3:34])[CH2:18]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[N:1]([CH2:4][C@@H:5]([NH:15][C:31]([C:29]1[S:30][C:26]([C:25]2[C:20]3[C@H:19]([CH3:34])[CH2:18][C@@H:17]([OH:16])[C:21]=3[N:22]=[CH:23][N:24]=2)=[CH:27][CH:28]=1)=[O:32])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[Cl:14])=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=NC[C@@H](N)Cc1ccc(Cl)cc1Cl
Reactant: C[C@@H]1C[C@@H](O)c2ncnc(-c3ccc(C(=O)O)s3)c21
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: C[C@@H]1C[C@@H](O)c2ncnc(-c3ccc(C(=O)N[C@H](CN=[N+]=[N-])Cc4ccc(Cl)cc4Cl)s3)c21
Temperature: 25 °C
Reaction time: 1 h
Yield: 11 %

Procedure:
(S)-1-Azido-3-(2,4-dichlorophenyl)propan-2-amine (20 mg, 0.0724 mmol) was added to a solution of 5-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)thiophene-2-carboxylic acid (35 mg, 0.145 mmol) in DCM (0.5 mL) DMF (125 μL) was added to solubilize the starting material completely. DIPEA (126 μL, 0.724 mmol) was added, followed by the addition of HBTU (30 mg, 0.079 mmol). The reaction mixture was stirred at room temperature for 1 hour. LC-MS of the reaction mixture showed no more starting material. The solvent was removed, and the resulting residue was purified by reversed phase HPLC to yield N—((S)-1-azido-3-(2,4-dichlorophenyl)propan-2-yl)-5-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)thiophene-2-carboxamide product as a solid (4 mg, 10%). m/z 504 (MH+).