Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[C:4]([CH3:11])[CH:3]=1.[Br:12]N1C(=O)CCC1=O.ClCCl>ClC(Cl)(Cl)Cl>[Br:1][C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[C:4]([CH2:11][Br:12])[CH:3]=1
Reactant: COC(=O)c1sc(Br)cc1C
Reactant: O=C1CCC(=O)N1Br
Solvent: ClCCl
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1sc(Br)cc1CBr
Temperature: 90 °C
Reaction time: 18 h

Procedure:
In a 100 mL round bottom flask, methyl 5-bromo-3-methylthiophene-2-carboxylate (1.50 g, 6.38 mmol) was dissolved in tetrachloromethane (30 mL). To above solution was added 1-bromopyrrolidine-2,5-dione (1.14 g, 6.38 mmol, 1.0 eq) and diphenylperoxyanhydride (0.155 g, 0.638 mmol, 0.1 eq). The reaction was stirred at 90° C. for 18 hr. To above reaction was added dichloromethane (30 mL), washed with aqueous sodium bicarbonate, brine and water. The organic phase was dried over MgSO4, filtered and concentrated. The crude was used in next step without purification. LC-MS (IE, m/z): 337.4 [M+N]+.
Reaction SMILES: C([Si:4]1([C:11]2[CH:16]=[CH:15]C=CC=2)[CH2:9][CH2:8][C:7](=O)[CH2:6][CH2:5]1)CC.Br[C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]([F:29])=[C:26]([F:28])[F:27])=[C:20]([F:30])[CH:19]=1>>[CH2:11]([Si@H:4]1[CH2:5][CH2:6][C@H:7]([C:18]2[CH:23]=[CH:22][C:21]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:29])=[C:26]([F:28])[F:27])=[C:20]([F:30])[CH:19]=3)=[C:20]([F:30])[CH:19]=2)[CH2:8][CH2:9]1)[CH2:16][CH3:15]
Reactant: CCC[Si]1(c2ccccc2)CCC(=O)CC1
Reactant: FC(F)=C(F)Oc1ccc(Br)cc1F
Product: CCC[Si@H]1CC[C@H](c2ccc(-c3ccc(OC(F)=C(F)F)c(F)c3)c(F)c2)CC1

Procedure:
The general procedure of Example 36 was repeated using 4-propyl-4-phenyl-4-silacyclohexanone instead of 4-pentyl-4-phenyl-4-silacyclohexanone and 4-bromo-2-fluoro-1-(1,2,2-trifluorovinyloxy)benzene instead of 4-bromo-2,6-difluoro-1-(1,2,2-trifluorovinyl)benzene, thereby obtaining the intended compound.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([O:19]C)[CH:13]=2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.Br>O>[Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([OH:19])[CH:13]=2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1
Reactant: COc1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl
Agent: Br
Solvent: O
Product: Oc1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl
Yield: 93.6 %

Procedure:
20.0 g (62.1 mmol) of 3-chloro-2-(4-chloro-3-methoxyphenyl)-5-trifluoromethylpyridine in 110 ml of 47% strength aqueous hydrobromic acid were refluxed for five hours. The reaction mixture was then diluted, while cooling in ice, with about 400 ml of water and extracted three times with 150 ml of methylene chloride each time. The combined organic phases were dried over sodium sulfate and evaporated to give a residue of 17.9 g (94%) of colorless crystals of melting point 105°-107° C.
Reaction SMILES: C(OC([NH:8][CH2:9][C@H:10]([N:15]1[CH2:20][CH2:19][N:18]([S:21]([CH2:24][CH:25]([CH3:27])[CH3:26])(=[O:23])=[O:22])[CH2:17][CH2:16]1)[C:11]([O:13][CH3:14])=[O:12])=O)(C)(C)C.[ClH:28].Cl.NC[C@H](N1CCN(S(CC(C)C)(=O)=O)CC1)C(OC)=O>>[ClH:28].[ClH:28].[NH2:8][CH2:9][C@H:10]([N:15]1[CH2:20][CH2:19][N:18]([S:21]([CH:24]=[C:25]([CH3:27])[CH3:26])(=[O:23])=[O:22])[CH2:17][CH2:16]1)[C:11]([O:13][CH3:14])=[O:12]
Reactant: COC(=O)[C@H](CNC(=O)OC(C)(C)C)N1CCN(S(=O)(=O)CC(C)C)CC1
Agent: COC(=O)[C@H](CN)N1CCN(S(=O)(=O)CC(C)C)CC1
Agent: Cl
Product: COC(=O)[C@H](CN)N1CCN(S(=O)(=O)C=C(C)C)CC1

Procedure:
In a manner analogous to example 3.3, using 785 mg (1.9 mmol) of methyl (S)-3-tert-butoxycarbonylamino-2-[4-(2-methylpropane-1-sulfonyl)piperazin-1-yl]propanoate, 621 mg (85%) of methyl (S)-3-amino-2-[4-(2-methylpropane-1-sulfonyl)piperazin-1-yl]propanoate dihydrochloride are obtained in the form of a solid.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:15](=[S:17])[NH:14][C:13](=[O:18])[N:12]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:11]=2[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].S(OC)(O[CH3:30])(=O)=O>O>[CH2:1]([N:8]1[C:16]2[C:15]([S:17][CH3:30])=[N:14][C:13](=[O:18])[N:12]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:11]=2[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COS(=O)(=O)OC
Reactant: CCCCCn1c(=O)[nH]c(=S)c2c1ncn2Cc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCn1c(=O)nc(SC)c2c1ncn2Cc1ccccc1
Temperature: 80 °C
Reaction time: 8 h
Yield: 94.9 %

Procedure:
To a mixture of 7-benzyl-3-pentyl-6-thioxo-1,3,6,7-tetrahydro-2H-purin-2-one (5.3 g, 16 mmol) in a solution of sodium hydroxide in water (2 M, 50.0 mL) was added dimethyl sulfate (2.3 mL, 24 mmol). The reaction mixture was stirred at 80° C. overnight, quenched with acetic acid and extracted with dichloromethane (DCM). The organic layer was dried and concentrated to provide the desired product (5.2 g, 98% yield). LCMS calculated for C18H23N4OS (M+H): 343.2. found: 343.1.
Reaction SMILES: Cl.[CH3:2][O:3][NH:4][CH3:5].CCN(CC)CC.[CH2:13]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH2:26][CH:25]([C:29]([OH:31])=O)[CH2:24]1)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CCN=C=NCCCN(C)C.Cl>ClCCl.CCOC(C)=O>[CH3:2][O:3][N:4]([CH3:5])[C:29]([CH:25]1[CH2:26][CH2:27][CH2:28][N:23]([C:21]([O:20][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[O:22])[CH2:24]1)=[O:31]
Reactant: CNOC
Reactant: O=C(O)C1CCCN(C(=O)OCc2ccccc2)C1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CON(C)C(=O)C1CCCN(C(=O)OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 85.5 %

Procedure:
A 1000-mL 3-necked round-bottom flask was charged with a solution of N-methoxymethan amine hydrochloride (21.45 g, 217.7 mmol, 1.10 equiv, 99%) in dichloromethane (DCM) (250 mL). To the mixture was added Et3N (22.22 g, 217.80 mmol, 1.10 equiv, 99%) at 0-10° C., followed by addition 1-(benzyloxycarbonyl)piperidine-3-carboxylic acid (58 g, 220.3 mmol, 1.00 equiv) in dichloromethane (150 mL) drop wise at 2° C. over 2 hr period. To this mixture was added EDC.HCl (42.02 g, 217.80 mmol, 1.10 equiv, 99%) in several batches while maintaining the temperature below 5° C. The resulting solution was allowed to stir at room temperature overnight. The progress was monitored by TLC (EtOAc: PE=1:1). Upon completion, the reaction was then quenched by the addition of water (500 mL). The resulting mixture was then extracted with dichloromethane (2×500 mL). Combined organic layers were dried over anhydrous magnesium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by a silica gel column chromatography eluted with ethyl acetate/petroleum ether (1:10) affording benzyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate as a white syrup (57 g, 83%).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.C(N=C=NCCCN(C)C)C.[CH3:19][O:20][C:21]1[C:22](=[O:45])[C:23]([CH3:44])=[C:24]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:40][CH:41]([CH3:43])[CH3:42])=[C:35]([CH:39]=2)[C:36](O)=[O:37])[C:25](=[O:29])[C:26]=1[O:27][CH3:28]>C(Cl)Cl>[CH3:19][O:20][C:21]1[C:22](=[O:45])[C:23]([CH3:44])=[C:24]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:40][CH:41]([CH3:42])[CH3:43])=[C:35]([CH:39]=2)[C:36]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:37])[C:25](=[O:29])[C:26]=1[O:27][CH3:28]
Reactant: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)C)c(C(=O)O)c2)=C(C)C1=O
Reactant: C1CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)C)c(C(=O)N3CCCCC3)c2)=C(C)C1=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 38.6 %

Procedure:
Piperidine (0.030 g, 0.353 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.101 g, 0.529 mmol) were added to a methylene chloride solution (5 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-isopropoxybenzoic acid (0.066 g, 0.176 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (hexand:ethyl acetate=1:6) to obtain the titled compound (0.030 g, 0.068 mmol, 39%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[H-].[Na+].Cl[C:16]1[C:21]([NH2:22])=[C:20](Cl)[N:19]=[CH:18][N:17]=1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:16]2[C:21]([NH2:22])=[C:20]([O:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C:9]([F:12])([F:10])[F:11])[CH:4]=3)[N:19]=[CH:18][N:17]=2)=[CH:4][C:3]=1[C:9]([F:10])([F:11])[F:12]
Reactant: Oc1ccc(F)c(C(F)(F)F)c1
Reactant: Nc1c(Cl)ncnc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Nc1c(Oc2ccc(F)c(C(F)(F)F)c2)ncnc1Oc1ccc(F)c(C(F)(F)F)c1
Temperature: 10 °C
Reaction time: 1 h

Procedure:
Dissolved in 70 ml DMF, 40.8 g 4-fluoro-3-(trifluoromethyl)-phenol are stirred under an inert gas atmosphere and cooled to 10° C. To this, 5.8 g sodium hydride are added slowly under vigorous stirring. The mixture is then allowed to warm up to room temperature and stirred for 1 h. Then, a solution of 19.9 g 4,6-Dichloro-5-aminopyrimidine in 50 ml DMF is added dropwise and the reaction mixture is heated for 24 h at 80° C. After quenching with water and concentration under reduced pressure the crude mixture is extracted twice with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride and finally dried over magnesium sulfate and charcoal. The dark brown oily residue is dissolved in 100 ml diethylether and treated with 100 ml hexane. The resulting title compound crystallizes as a colorless solid with a melting point of 104-105° C.
Reaction SMILES: [CH2:1]([N:8]1CCN(C2SC(C(O)=O)=C(C)N=2)C1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:23]([C@@H:30]1[CH2:34][N:33]([C:35]2[S:36][C:37]([C:41]([OH:43])=O)=[C:38]([CH3:40])[N:39]=2)[C:32](=[O:44])[NH:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N)C1C=CC=CC=1>>[CH2:1]([NH:8][C:41]([C:37]1[S:36][C:35]([N:33]2[CH2:34][C@@H:30]([CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[NH:31][C:32]2=[O:44])=[N:39][C:38]=1[CH3:40])=[O:43])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1nc(N2C[C@@H](Cc3ccccc3)NC2=O)sc1C(=O)O
Reactant: Cc1nc(N2CCN(Cc3ccccc3)C2=O)sc1C(=O)O
Solvent: NCc1ccccc1
Product: Cc1nc(N2C[C@@H](Cc3ccccc3)NC2=O)sc1C(=O)NCc1ccccc1
Yield: 10 %

Procedure:
Following the procedure as describe in Example 9, making variations as required to replace 2-(3-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid with (R)-2-(4-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid to react with benzylamine, the title compound was obtained as a white powder in 10% yield: mp 212-214° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.43 (t, J=5.7 Hz, 1H), 8.02 (br s, 1H), 7.30-7.01 (m, 10H), 4.31 (d, J=5.7 Hz, 2H), 4.14-4.05 (m, 1H), 3.91 (t, J=10.2 Hz, 1H), 3.69-3.64 (m, 1H), 2.90-2.73 (m, 2H), 2.39 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 162.1, 157.4, 156.2, 151.4, 140.1, 136.9, 129.8, 128.8, 128.6, 127.6, 127.1, 127.0, 118.0, 50.4, 48.9, 43.0, 41.1, 17.4; MS (ES+) m/z 407.0 (M+1).
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([F:12])([F:11])[F:10])=[N:7][CH:8]=1.[C-:13]#[N:14].[K+]>C(O)C.O>[F:10][C:9]([F:12])([F:11])[C:6]1[N:7]=[CH:8][C:3]([CH2:2][C:13]#[N:14])=[CH:4][CH:5]=1
Reactant: FC(F)(F)c1ccc(CCl)cn1
Reactant: [C-]#N
Agent: [K+]
Solvent: CCO
Solvent: O
Product: N#CCc1ccc(C(F)(F)F)nc1
Temperature: 90 °C
Reaction time: 3 h
Yield: 52.8 %

Procedure:
5-Chloromethyl-2-trifluoromethylpyridine (19.5 g, 99.7 mmol) in ethanol (160 mL) was added to a solution of potassium cyanide (9.74 g, 150 mmol) in water (80 mL) at 90° C. over 30 minutes. The mixture was stirred at 90° C. for 3 hours. Most of the ethanol was removed under reduced pressure and the aqueous layer was extracted with AcOEt (3×100 mL). The combined organic extracts were washed with water, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (30% AcOEt in hexanes) to afford (6-trifluoromethylpyridin-3-yl)-acetonitrile as a brown oil (9.79 g, 75%). 1H NMR (400 MHz, CDCl3) δ ppm 8.63 (s, 1 H), 7.90 (d, J=8.0 Hz, 1 H), 7.70 (d, J=8.0 Hz 1 H), 3.88 (s, 2 H). 19F NMR (400 MHz, CDCl3):168 cm−1. MS m/z 187.14
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][O:11][C:12](=[O:23])OC2C=CC([N+]([O-])=O)=CC=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[NH2:24][C@H:25]([C:29]([OH:31])=[O:30])[CH:26]([CH3:28])[CH3:27].C(N(CC)CC)C.C(O)C>O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:10][O:11][C:12]([NH:24][C@H:25]([C:29]([OH:31])=[O:30])[CH:26]([CH3:28])[CH3:27])=[O:23])=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=C(OCc1ccc([N+](=O)[O-])cc1)Oc1ccc([N+](=O)[O-])cc1
Reactant: CC(C)[C@H](N)C(=O)O
Solvent: CCN(CC)CC
Solvent: O
Solvent: CCO
Product: CC(C)[C@H](NC(=O)OCc1ccc([N+](=O)[O-])cc1)C(=O)O
Yield: 35.7 %

Procedure:
The title compound is prepared by the procedure of Example 255 using 14.73 g of product from Example 254, 5.42 g of L-valine, 12.75 ml of triethylamine and 556 ml of 4:1 ethyl alcohol:water to give 4.89 g of the desired product after chromatography.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[N:5][N:4]=[C:3]1[SH:7].[H-].[Na+].Cl[C:11]1[C:12]([C:17]#[N:18])=[N:13][CH:14]=[CH:15][N:16]=1>CN(C=O)C.C1C=CC=CC=1>[CH3:1][N:2]1[CH:6]=[N:5][N:4]=[C:3]1[S:7][C:11]1[C:12]([C:17]#[N:18])=[N:13][CH:14]=[CH:15][N:16]=1
Reactant: N#Cc1nccnc1Cl
Reactant: Cn1cnnc1S
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: Cn1cnnc1Sc1nccnc1C#N
Temperature: 25 °C
Reaction time: 4 h

Procedure:
The title compound was prepared according to Example 1 by using 4-methyl-4H-1,2,4-triazole-3-thiol (230.5 mg, 2.00 mmol), NaH (60% dispersion in mineral oil, 88 mg, 2.20 mmol), and 3-chloropyrazine-2-carbonitrile (280 mg, 2.00 mmol) in DMF and benzene (6 ml, 1/1) by stirring at room temperature under nitrogen atmosphere for 4 hr.
Reaction SMILES: [CH:1]([C:5]1[CH:6]=[C:7](/[CH:19]=[CH:20]/[C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)[CH:8]=[C:9]2[C:14]=1[O:13][C:12](=[O:15])[C:11]([C:16](O)=[O:17])=[CH:10]2)([CH2:3][CH3:4])[CH3:2].S(Cl)(Cl)=O.[CH2:34]([NH2:36])[CH3:35]>C1(C)C=CC=CC=1>[CH:1]([C:5]1[CH:6]=[C:7](/[CH:19]=[CH:20]/[C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)[CH:8]=[C:9]2[C:14]=1[O:13][C:12](=[O:15])[C:11]([C:16]([NH:36][CH2:34][CH3:35])=[O:17])=[CH:10]2)([CH2:3][CH3:4])[CH3:2]
Reactant: CCC(C)c1cc(/C=C/C(=O)c2ccc(C)cc2)cc2cc(C(=O)O)c(=O)oc12
Reactant: CCN
Solvent: Cc1ccccc1
Solvent: O=S(Cl)Cl
Product: CCNC(=O)c1cc2cc(/C=C/C(=O)c3ccc(C)cc3)cc(C(C)CC)c2oc1=O
Reaction time: 0.58 h

Procedure:
To a suspension of (E)-8-sec-butyl-2-oxo-6-(3-oxo-3-p-tolylprop-1-enyl)-2H-chromene-3-carboxylic acid of the formula (V) (0.5 g, 1.28 mmol) in toluene (15 mL), added thionyl chloride (1.0 mL), was refluxed for 3 h. The resulting solution was evaporated to dryness under reduced pressure, and the residue was dispersed in toluene (15 mL). The solvent was eliminated under reduced pressure. Dispersion in toluene and solvent elimination was repeated twice. The residue was dissolved toluene (10 mL) and added with stirring to a solution of the ethyl amine (0.06 g, 1.28 mmol). After 35 min at room temperature, the solvent was removed by evaporation under reduced pressure and extracted 3-fold with CHCl3 (20 mL). The combined organic layers were dried on Na2SO4, filtered, and concentrated to dryness under reduced pressure. The residue was chromatographed over silica gel (SiO2, 230-400 flash), eluting with a gradient of 20% ethyl acetate in hexane to 40% ethyl acetate in hexane, which upon concentration provides (E)-8-sec-butyl-N-ethyl-2-oxo-6-(3-oxo-3-p-tolylprop-1-enyl)-2H-chromene-3-carboxamide (General Formula VI). (0.34 g, 64% yield). White solid, m. p. 162-163° C.; 1H NMR (CDCl3 300 MHz): δ 8.93 (s, 1H), 7.96 (d, J=8.2 Hz, 2H), 7.83-7.76 (m, 3H), 7.54 (d, J=15.7 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 3.57-3.39 (m, 3H), 2.45 (s, 3H), 1.80-1.73 (m, 2H), 1.34 (d, J=6.9 Hz, 3H), 1.28 (t, J=7.3 Hz, 3H). 0.91 (t, J=7.3 Hz, 3H): 13C NMR (CDCl3, 75 MHz): δ 189.6, 161.2, 161.1, 153.1, 148.5, 144.1, 142.3, 136.5, 135.4, 132.2, 131.4, 128.8, 127.1, 123.2, 119.1, 119.0, 122.8, 34.9, 33.7, 29.8, 21.8, 20.6, 14.8, 12.1; ESI-MS (m/z): 418(M+H)+.
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][NH2:5].[CH2:6]([N:10]=[C:11]=[O:12])[CH2:7][CH2:8][CH3:9]>O1CCCC1>[CH2:6]([NH:10][C:11]([N:4]([CH2:3][CH2:2][OH:1])[NH2:5])=[O:12])[CH2:7][CH2:8][CH3:9]
Reactant: CCCCN=C=O
Reactant: NNCCO
Solvent: C1CCOC1
Product: CCCCNC(=O)N(N)CCO
Temperature: 25 °C

Procedure:
To 7.61 g (0.1 moles) 2-hydroxyethylhydrazine in 150 mL tetrahydrofuran was added dropwise over a period of about 1/2 hour with stirring 9.91 g (0.1 mole) butylisocyanate in 50 mL tetrahydro-furan. At the end of the addition period stirring was continued until the solution cooled to room temperature. A small amount of precipitate was removed by filtration, and the solvent was evaporated to yield a viscous pale oil, N-butyl-1-(2-hydroxyethyl)hydrazinecarboxamide quantitatively. This structure was confirmed by NMR analysis.
Reaction SMILES: [Cl-].[CH3:2][N:3]([S:7]([CH3:10])(=[O:9])=[O:8])[CH2:4][CH2:5][NH3+:6].F[C:12]1[C:13]([C:18]#[N:19])=[N:14][CH:15]=[CH:16][CH:17]=1.CCN(C(C)C)C(C)C>CS(C)=O>[C:18]([C:13]1[C:12]([NH:6][CH2:5][CH2:4][N:3]([CH3:2])[S:7]([CH3:10])(=[O:9])=[O:8])=[CH:17][CH:16]=[CH:15][N:14]=1)#[N:19]
Reactant: N#Cc1ncccc1F
Reactant: CN(CC[NH3+])S(C)(=O)=O
Agent: [Cl-]
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CN(CCNc1cccnc1C#N)S(C)(=O)=O

Procedure:
In a manner similar to that described for Example 2, 2-[methyl(methylsulfonyl)amino]ethanaminium chloride (4 g, 25.4 mmol) was dissolved in DMSO (20 mL) and treated with 3-fluoro-2-cyanopyridine (2.5 g, 21.2 mmol) and Hunig's base (4.4 mL, 25.4 mmol) and heated to 90 degrees under pressure. The product was isolated as an oily off-white solid.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]4[O:21][C:20]([NH:22][CH:23]([CH3:25])[CH3:24])=[N:19][N:18]=4)[CH:15]=3)[N:10](S(C3C=CC(C)=CC=3)(=O)=O)[CH:9]=2)[N:3]=1.[CH3:36][O-:37].[Na+]>CO>[CH:23]([NH:22][C:20]1[O:21][C:17]([C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[NH:10][CH:9]=[C:8]3[C:4]2[N:3]=[C:2]([O:37][CH3:36])[CH:7]=[CH:6][N:5]=2)=[N:18][N:19]=1)([CH3:24])[CH3:25]
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3nccc(Cl)n3)c3cc(-c4nnc(NC(C)C)o4)ccc32)cc1
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1ccnc(-c2c[nH]c3ccc(-c4nnc(NC(C)C)o4)cc23)n1
Temperature: 100 °C
Yield: 61.2 %

Procedure:
A glass microwave reaction vessel was charged with 5-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (50 mg, 0.098 mmol) and sodium methoxide (18.57 mg, 0.344 mmol, Alfa Aesar) in MeOH (1 mL). The reaction was stirred and heated in a Initiator microwave reactor at 85° C. for 30 min and 100° C. for 1 h. The solvent was removed and the residue was purified with RP-HPLC (eluent: 10-50% MeCN in water with 0.1% TFA). The fractions containing the product were combined and concentrated to remove AcCN. The remaining mixture was neutralized with NH4OH and filtered and dried to give N-isopropyl-5-(3-(4-methoxypyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (21.0 mg, 0.060 mmol, 61.0%) as an off-white solid. MS (ESI, pos. ion) m/z: 351.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.98 (1H, br. s.), 9.04 (1H, s), 8.52 (1H, d, J=5.7 Hz), 8.32 (1H, s), 7.69 (1H, d, J=8.6 Hz), 7.58 (2H, dd, J=13.4, 7.9 Hz), 6.68 (1H, d, J=5.7 Hz), 4.09 (3H, s), 3.66-3.82 (1H, m), 1.23 (6H, d, J=6.5 Hz)
Reaction SMILES: [CH:1]1([NH:4][CH:5]2[CH2:10][CH2:9][N:8]([C:11]3[O:15][N:14]=[C:13]([CH:16]([CH3:18])[CH3:17])[N:12]=3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.[CH3:19][C:20]1[N:21]([C:25]2[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=2)[CH:22]=[CH:23][N:24]=1>>[CH:1]1([N:4]([CH:5]2[CH2:10][CH2:9][N:8]([C:11]3[O:15][N:14]=[C:13]([CH:16]([CH3:18])[CH3:17])[N:12]=3)[CH2:7][CH2:6]2)[C:29](=[O:30])[C:28]2[CH:27]=[CH:26][C:25]([N:21]3[CH:22]=[CH:23][N:24]=[C:20]3[CH3:19])=[CH:33][CH:32]=2)[CH2:2][CH2:3]1
Reactant: Cc1nccn1-c1ccc(C(=O)O)cc1
Reactant: CC(C)c1noc(N2CCC(NC3CC3)CC2)n1
Product: Cc1nccn1-c1ccc(C(=O)N(C2CC2)C2CCN(c3nc(C(C)C)no3)CC2)cc1

Procedure:
The title compound is prepared from cyclopropyl-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yl]-amine and 4-(2-methyl-imidazol-1-yl)-benzoic acid following a procedure analogous to that described in Example 90. LC (method 19): tR=3.46 min; Mass spectrum (ESI+): m/z=435 [M+H]+.
Reaction SMILES: O1CCC[CH2:2]1.Br[C:7]1[CH:8]=[C:9]([CH:12]=[C:13]([O:17][CH3:18])[C:14]=1[O:15][CH3:16])[C:10]#[N:11].CB1OB(C)OB(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.C(OCC)(=O)C>[CH3:18][O:17][C:13]1[CH:12]=[C:9]([CH:8]=[C:7]([CH3:2])[C:14]=1[O:15][CH3:16])[C:10]#[N:11]
Reactant: COc1cc(C#N)cc(Br)c1OC
Reactant: C1CCOC1
Agent: CB1OB(C)OB(C)O1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: O
Product: COc1cc(C#N)cc(C)c1OC
Temperature: 100 °C
Reaction time: 4 h

Procedure:
50 mg [1,1″-Bis(diphenylphosphino)ferrocene]dichloropalladium (II) and 5 mL tetrahydrofuran was stirred for 10 min at ambient temperature before 500 mg 3-bromo-4,5 dimethoxybenzonitrile, 0.1 mL trimethylboroxine and 0.85 g cesium carbonate as a solution in 1 mL water were added. The suspension was stirred at 100° C. for 4 h and then diluted with water and ethyl acetate. The phases were separated and the water phase was extracted with additional ethyl acetate (×2). The organic phases were combined, dried over magnesium sulfate and concentrated. The residue was purified with silica gel chromatography (SiO2:cyclohexane/ethyl acetate 9:1 to 7:3) to provide 4.17.
Reaction SMILES: Br[C:2]1[N:24]=[C:5]2[N:6]=[C:7]([C:16]3[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=3)[C:8]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[CH:9][N:4]2[N:3]=1.[CH3:25][Si:26]([CH3:43])([CH3:42])[C:27]#[C:28][Sn](CCCC)(CCCC)CCCC>C1(C)C=CC=CC=1.O.ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:10]1([C:8]2[C:7]([C:16]3[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=3)=[N:6][C:5]3[N:4]([N:3]=[C:2]([C:28]#[C:27][Si:26]([CH3:43])([CH3:42])[CH3:25])[N:24]=3)[CH:9]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=Cc1ccc(-c2nc3nc(Br)nn3cc2-c2ccccc2)cc1
Reactant: CCCC[Sn](C#C[Si](C)(C)C)(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: O
Product: C[Si](C)(C)C#Cc1nc2nc(-c3ccc(C=O)cc3)c(-c3ccccc3)cn2n1

Procedure:
300 mg 4-(2-bromo-6-phenyl[1,2,4]triazolo[1,5-a]pyrimidin-5-yl)benzaldehyde (prepared as described under example 53), 613 mg trimethyl[(tributylstannyl)ethynyl]silane and 46 mg Pd(PPh3)4 are suspended in 12 ml toluene under a nitrogen atmosphere. The mixture is heated (microwave irradiation) to 120° C. for 1 h. This mixture is worked up by diluting with water and extraction with dichloromethane. The organic layers are dried over Na2SO4 and concentrated to yield the crude product, which is purified by chromatography on silica gel (ethyl acetate/dichloromethane).