Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5]Br)[CH3:2].[CH2:10]([NH:12][CH2:13][CH3:14])[CH3:11]>>[CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][N:12]([CH2:13][CH3:14])[CH2:10][CH3:11])[CH3:2]
Reactant: CCNCC
Reactant: CCOC(CBr)OCC
Product: CCOC(CN(CC)CC)OCC
Temperature: 40 °C
Reaction time: 8 h
Yield: 72.8 %

Procedure:
Bromoacetaldehyde diethylacetal, 52.4 g (0.26 mol), was mixed carefully with approximately 70.7 g (0.967 mol) diethylamine and stirred at 40° C. overnight. The reaction mixture was concentrated under reduced pressure and the residue dissolved in water and basified with cold 5N sodium hydroxide. The reaction mixture was extracted twice with diethyl ether, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a tan oil. Distillation gave 35.8 g (72.8%) diethylaminoacetaldehyde diethylacetal as a clear liquid. B.p. 65°-75° C. @ 1.0 mmHg.
Reaction SMILES: [O:1]([CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19](Cl)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCCl>[C:19]([C:5]1[CH:4]=[CH:3][C:2]([O:1][CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[CH:15][C:16]([C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:17][CH:18]=2)=[CH:7][CH:6]=1)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: c1ccc(OCCCCOc2ccccc2)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Product: O=C(c1ccccc1)c1ccc(OCCCCOc2ccc(C(=O)c3ccccc3)cc2)cc1

Procedure:
1,4-Diphenoxy-n-butane (24.2 g) and benzoyl chloride (29 g) are reacted in 250 ml of 1,2-dichloroethane in the presence of aluminum chloride (28 g) for 4 hours at 60° to yield 18.3 g (41% of theory) of colorless crystals mp 163°-4°. Calculated for C30H26O4 : C, 79.98% H, 5.82%. Found: C, 80.16%; H, 5.98%.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11]C(N)=[CH:9][C:3]=1[C:4]([NH:6][CH2:7][CH3:8])=[O:5].C(=O)([O-])[O-].[K+].[K+].CI.O.[CH3:23][N:24]([CH:26]=O)[CH3:25]>>[CH2:7]([NH:6][C:4](=[O:5])[C:3]1[CH:9]=[C:26]([N:24]([CH3:23])[CH3:25])[CH:11]=[CH:12][C:2]=1[Cl:1])[CH3:8]
Reactant: CCNC(=O)c1cc(N)ccc1Cl
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CI
Product: CCNC(=O)c1cc(N(C)C)ccc1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 29 %

Procedure:
A mixture of the above amine (3 g, 0.015 mol), potassium carbonate (3.8 g, 0.028 mol) and MeI (1.4 mL, 0.022 mol) in DMF stirred at RT overnight. The reaction mixture was poured into water and extracted with ether. The ether layer was washed with water and brine, dried (MgSO4) and concentrated to give an oil. Purification by flash chromatography (0-50% ethyl acetate/hexanes) gave N-ethyl 2-chloro-5-(dimethylamino)benzamide as a yellow solid in 29% yield.
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:21])[N:4]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:5]([CH3:15])=[CH:6][C:7]=1[S:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.ClC(O[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=O>>[CH3:15][C:5]1[N:4]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:3](=[O:21])[C:2]([NH:1][C:17]([O:19][CH2:20][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[O:18])=[C:7]([S:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: COC(=O)Cn1c(C)cc(Sc2ccccc2)c(N)c1=O
Product: COC(=O)Cn1c(C)cc(Sc2ccccc2)c(NC(=O)OCCc2ccccc2)c1=O

Procedure:
1.7 g (5.6 mmol) of methyl 3-amino-6-methyl-2-oxo-4-(phenylthio)-1,2-dihydropyridine-1-acetate are treated with 1.2 ml (8.4 mmol) of phenylmethyl chloroformate under the conditions described in Example 3.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]([CH2:17][C:18]([F:21])([F:20])[F:19])[C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([C:13]([F:16])([F:15])[F:14])[CH:6]=1.O[C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[CH:25][CH:24]=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1.C(P(CCCC)CCCC)CCC>C1COCC1.CCOC(C)=O>[C:9]([C:8]1[CH:11]=[CH:12][C:5]([N:4]([CH2:17][C:18]([F:19])([F:20])[F:21])[CH2:3][CH2:2][O:1][C:23]2[CH:24]=[CH:25][C:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[CH:27][CH:28]=2)=[CH:6][C:7]=1[C:13]([F:15])([F:16])[F:14])#[N:10]
Reactant: N#Cc1ccc(N(CCO)CC(F)(F)F)cc1C(F)(F)F
Reactant: CC(C)(C)OC(=O)Nc1ccc(O)cc1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)Nc1ccc(OCCN(CC(F)(F)F)c2ccc(C#N)c(C(F)(F)F)c2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 82.6 %

Procedure:
To a solution of 4-[(2-hydroxyethyl)(2,2,2-trifluoroethyl)amino]-2-(trifluoromethyl)benzonitrile (0.100 g, 0.32 mmol), 1,1-dimethylethyl (4-hydroxyphenyl)carbamate (0.0737 g, 0.35 mmol) and ADDP (0.121 g, 0.48 mmol) in THF (3.5 mL) at rt was added tri-n-butylphosphine (0.12 mL, 0.48 mmol). The resulting mixture was stirred 1 hour at rt and diluted with EtOAc until homogeneous. The resulting solution was extracted with 1 N NaOH (×2), washed (water, brine), dried over Na2SO4 and filtered. The filtrate was adsorbed onto a minimal amount of silica gel and purified by flash chromatography (EtOAc/hexanes), affording 0.133 g of the title compound as a colorless gum: 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J=9.0 Hz, 1H), 7.26 (app. d, J=8.3 Hz, 2H), 7.16 (d, J=2.3 Hz, 1H), 6.98 (dd, J=9.0, 2.5 Hz, 1H), 6.80-6.75 (m, 2H), 6.38 (bs, 1H), 4.24-4.14 (m, 4H), 3.97 (t, J=5.1 Hz, 2H), 1.50 (s, 9H); MS (ESI) m/z 502 (M−1).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C([O-])(O)=O.[Na+].[CH3:18][N:19](C=O)C>CC#N>[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:18]#[N:19])=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: CN(C)C=O
Reactant: O=[N+]([O-])c1ccc2cc[nH]c2c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Product: N#Cc1c[nH]c2cc([N+](=O)[O-])ccc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 82 %

Procedure:
To a solution of 6-nitroindole (4.86 g 30 mmol) in DMF (24.3 mL) and CH3CN (243 mL) was added dropwise a solution of C1SO2NCO (5 mL, 57 mmol) in CH3CN (39 mL) at 0° C. After addition, the reaction was allowed to warm to room temperature and stirred for 2 h. The mixture was poured into ice-water, basified with sat. NaHCO3 solution to pH 7-8 and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and concentrated to give 6-nitro-1H-indole-3-carbonitrile (4.6 g, 82%).
Reaction SMILES: [CH3:1][S:2]([NH:5][C:6]1[CH:14]=[C:13]2[C:9]([CH:10]=[C:11]([C:15]([O:17]C)=[O:16])[NH:12]2)=[CH:8][CH:7]=1)(=[O:4])=[O:3].[OH-].[Li+]>CO.O>[CH3:1][S:2]([NH:5][C:6]1[CH:14]=[C:13]2[C:9]([CH:10]=[C:11]([C:15]([OH:17])=[O:16])[NH:12]2)=[CH:8][CH:7]=1)(=[O:3])=[O:4]
Reactant: COC(=O)c1cc2ccc(NS(C)(=O)=O)cc2[nH]1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CS(=O)(=O)Nc1ccc2cc(C(=O)O)[nH]c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.9 %

Procedure:
To 333 mg (1.24 mmol) of methyl 6-[(methylsulfonyl)amino]-1H-indole-2-carboxylate dissolved in 8 mL methanol was added 130 mg (3.10 mmol) lithium hydroxide dissolved in 2 mL water. The mixture was stirred at room temperature overnight, partitioned between ethyl acetate and 1 N hydrochloric acid, was dried over magnesium sulfate and concentrated to obtain 230 mg of 6-[(methylsulfonyl)amino]-1H-indole-2-carboxylic acid.
Reaction SMILES: [C:1]([C:3]1[CH:26]=[CH:25][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13](/[CH:17]=[C:18]4/[C:19](=[O:24])[NH:20][C:21](=[O:23])[S:22]/4)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[C:5]([C:27]([F:30])([F:29])[F:28])[CH:4]=1)#[N:2].Br[CH2:32][C:33]([O:35]C(C)(C)C)=[O:34]>>[C:1]([C:3]1[CH:26]=[CH:25][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13](/[CH:17]=[C:18]4/[C:19](=[O:24])[N:20]([CH2:32][C:33]([OH:35])=[O:34])[C:21](=[O:23])[S:22]/4)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[C:5]([C:27]([F:30])([F:29])[F:28])[CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(Cn2ncc3cc(/C=C4\SC(=O)NC4=O)ccc32)c(C(F)(F)F)c1
Reactant: CC(C)(C)OC(=O)CBr
Product: N#Cc1ccc(Cn2ncc3cc(/C=C4\SC(=O)N(CC(=O)O)C4=O)ccc32)c(C(F)(F)F)c1

Procedure:
[(5Z)-5-({1-[4-Cyano-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-2,4-dioxo-1,3-thiazolidin-3-yl]acetic acid was prepared from [(5Z)-5-({1-[4-cyano-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-2,4-dioxo-1,3-thiazolidine (from Example 246) and tert-butyl bromoacetate following General Procedure I.
Reaction SMILES: [C:1]1([C:7]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=[C:9]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]4[OH:32])=[CH:21][C:20]=3[OH:33])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:34](Cl)(=[O:36])[CH3:35].N1C=CC=CC=1>C1(C)C=CC=CC=1>[C:13]1([C:11]2[N:12]=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:8]=[C:9]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]4[O:32][C:34](=[O:36])[CH3:35])=[CH:21][C:20]=3[OH:33])[N:10]=2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: Oc1cc(OC2CCCCC2O)ccc1-c1nc(-c2ccccc2)nc(-c2ccccc2)n1
Reactant: CC(=O)Cl
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CC(=O)OC1CCCCC1Oc1ccc(-c2nc(-c3ccccc3)nc(-c3ccccc3)n2)c(O)c1
Reaction time: 6 h

Procedure:
A mixture of 13.0 g (29.6 mmol) of 2,4-diphenyl-6-(2'-hydroxy4'-(2"-hydroxycyclohexyloxy)phenyl)-1,3,5-triazine, 7.0 g (89.2 mmol) of acetyl chloride (Fluka, 99%) and 0.6 g (7.6 mmol) of pyridine in 140 ml of toluene (Merck, 99.5%) is stirred under nitrogen and held at 50° C. for 6 h.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5]([NH:7][C:8]1[CH:44]=[CH:43][C:11]([CH:12]=[CH:13][C:14]([NH:16][CH2:17][C:18]([N:20]([C:22]2[C:23]([Cl:42])=[C:24]([C:38]([Cl:41])=[CH:39][CH:40]=2)[CH2:25][O:26][C:27]2[CH:28]=[CH:29][CH:30]=[C:31]3[C:36]=2[N:35]=[C:34]([CH3:37])[CH:33]=[CH:32]3)[CH3:21])=[O:19])=[O:15])=[CH:10][C:9]=1[CH3:45])=[O:6].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Cl:42][C:23]1[C:22]([N:20]([CH3:21])[C:18](=[O:19])[CH2:17][NH:16][C:14](=[O:15])[CH:13]=[CH:12][C:11]2[CH:43]=[CH:44][C:8]([N:7]3[CH2:2][CH2:3][CH2:4][C:5]3=[O:6])=[C:9]([CH3:45])[CH:10]=2)=[CH:40][CH:39]=[C:38]([Cl:41])[C:24]=1[CH2:25][O:26][C:27]1[CH:28]=[CH:29][CH:30]=[C:31]2[C:36]=1[N:35]=[C:34]([CH3:37])[CH:33]=[CH:32]2
Reactant: Cc1ccc2cccc(OCc3c(Cl)ccc(N(C)C(=O)CNC(=O)C=Cc4ccc(NC(=O)CCCBr)c(C)c4)c3Cl)c2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc2cccc(OCc3c(Cl)ccc(N(C)C(=O)CNC(=O)C=Cc4ccc(N5CCCC5=O)c(C)c4)c3Cl)c2n1
Temperature: 50 °C
Reaction time: 2 h
Yield: 73.8 %

Procedure:
To a solution of 8-[3-[N-[4-(4-bromobutyramido)-3-methylcinnamoylglycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2-methylquinoline (110 mg) in N,N-dimethylformamide was added potassium carbonate (64 mg) and the mixture was stirred for 2 hours at 50° C. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried and concentrated in vacuo. The residue was purified by preparative thin-layer chromatography (dichloromethane-methanol) to give 8-[2,6-dichloro-3-[N-methyl-N-[3-methyl-4-(2-oxopyrrolidin-1-yl)cinnamoylglycyl]amino]benzyloxy]-2-methylquinoline (72 mg) as an amorphous powder.
Reaction SMILES: [C:1]1(=[O:26])[N:5]([CH:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH3:20])=[CH:13][CH:12]=2)[CH2:7][C:8](O)=[O:9])[C:4](=[O:21])[C:3]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:2]12.C(N1C=CN=C1)([N:29]1C=CN=C1)=O.CN(C1C=CC=CN=1)C.[OH-].[NH4+]>O>[C:1]1(=[O:26])[N:5]([CH:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH3:20])=[CH:13][CH:12]=2)[CH2:7][C:8]([NH2:29])=[O:9])[C:4](=[O:21])[C:3]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:2]12
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CCCOc1ccc(C(CC(=O)O)N2C(=O)c3ccccc3C2=O)cc1
Agent: CN(C)c1ccccn1
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Product: CCCOc1ccc(C(CC(N)=O)N2C(=O)c3ccccc3C2=O)cc1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 36.4 %

Procedure:
To a stirred solution of 3-phthalimido-3(4-propoxyphenyl)propionic acid (1.41 g, 4.0 mmol) in 25 mL of under nitrogen was added carbonyldiimidazole (0.68 g, 4.2 mmol) followed by a catalytic amount of dimethylaminopyridine. The mixture was stirred for 45 minutes at room temperature. To the reaction mixture was then added concentrated ammonium hydroxide (0.29 mL, 4.4 mmol) and the reaction mixture was stirred for 30 minutes at room temperature. The mixture was then diluted with 10 mL of water and the tetrahydrofuran was removed in vacuo. The resulting slurry was filtered and the solid was washed with copious amounts of water. The solid was dried in vacuo (60° C., <1 mm) to afford 1.2 g of crude product. The crude product was purified by dissolving in 200 mL of ethyl acetate, stirring for 3 h and then concentrating to an 80 mL volume. The resulting slurry was filtered and the solid was washed with ethyl acetate (2×20 mL). The solid was air-dried to afford 0.513 g (36%) of 3-phthalimido-3-(4-propoxyphenyl)propionamide as a white powder: mp 109.5°-110.4° C.; 1H NMR (DMSO-d6, 250 MHz) δ 7.85 (br s, 4 H), 7.55 (br s, 1 H), 7.33 (d, 2 H, J=8 Hz), 6.75-7.00 (m, 3 H), 5.69 (t, 1 H, J=8 Hz), 3.88 (t, 2 H, J=6 Hz), 3.10-3.30 (m, 2 H), 1.60-1.80 (m, 2 H), 0.95 (t, 3 H, J=7 Hz); 13C NMR (DMSO-d6) δ 171.2, 167.7, 158.0, 134.5, 131.23, 131.19, 128.4, 123.1, 114.3, 68.9, 49.9, 36.9, 22.0, 20.4, 10.4; Anal. Calcd. for C20N2O4 0.37 H2O. Theoretical: C, 66.90; H, 5.61; N, 7.80. Found: C, 66.90; H, 5.52; N, 7.75.
Reaction SMILES: [OH:1][C:2]1[C:3]([C:17](=O)[CH3:18])=[N:4][N:5]([CH3:16])[C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH3:15])[CH3:14])=[CH:9][CH:8]=1.[NH:20]([C:22]([NH:24][C:25]1[CH:33]=[CH:32][C:28]([C:29]([OH:31])=[O:30])=[CH:27][CH:26]=1)=[S:23])[NH2:21].CN(C)C=O>Cl.O>[OH:1][C:2]1[C:3]([C:17](=[N:21][NH:20][C:22]([NH:24][C:25]2[CH:33]=[CH:32][C:28]([C:29]([OH:31])=[O:30])=[CH:27][CH:26]=2)=[S:23])[CH3:18])=[N:4][N:5]([CH3:16])[C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH3:15])[CH3:14])=[CH:9][CH:8]=1
Reactant: NNC(=S)Nc1ccc(C(=O)O)cc1
Reactant: CC(=O)c1nn(C)c(-c2ccc(C(C)C)cc2)c1O
Agent: Cl
Solvent: CN(C)C=O
Solvent: O
Product: CC(=NNC(=S)Nc1ccc(C(=O)O)cc1)c1nn(C)c(-c2ccc(C(C)C)cc2)c1O
Yield: 72 %

Procedure:
1-[4-Hydroxy-5-(4-isopropylphenyl)-1-methyl-1H-pyrazol-3-yl]ethanone (0.116 mmol, 29.9 mg) and 4-hydrazinocarbonothioylaminobenzoic acid (0.116 mmol, 24.5 mg) were stirred with dimethylformamide (2 mL) and two drops of concentrated hydrochloric acid at room temperature for 24 hours. After addition of water, the precipitated yellow solid was recovered by filtration, washed with water and dried by means of a vacuum pump. The resulting solid was stirred with chloroform/n-hexane for a while, then recovered by filtration and dried by means of a vacuum pump to give the desired product as a pale yellow solid (37.7 mg, yield 72%).
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3C=CC([CH:4]2[CH:3]=[CH:2]1)C3.C[SiH:12]([Cl:14])[Cl:13].CCCCCCCCCCCCCCCC>C1(C)C=CC=CC=1>[CH:5]1([CH2:6][SiH:12]([Cl:14])[Cl:13])[CH2:4][CH2:3][CH:2]=[CH:1]1
Reactant: C[SiH](Cl)Cl
Reactant: C1=CC2C3C=CC(C3)C2C1
Solvent: Cc1ccccc1
Solvent: CCCCCCCCCCCCCCCC
Product: Cl[SiH](Cl)CC1C=CCC1
Reaction time: 1 h
Yield: 781.2 %

Procedure:
As described in Example 2, 1.49 g (0.0113 mol) of dicyclopentadiene, 10.79 g (0.0902 mol) of methyldichlorosilane, 5 mL of toluene and 2 mL of hexadecane were placed in a reactor. The reactor was sealed and the reaction was performed at 250° C. for 1 hour. Products were subject to simple vacuum distillation, thereby providing a mixture (15.99 g) of (2-cyclopentenyl)methyldichlorosilane (1.2 g, 29%), unreacted methyldichlorosilane, toluene and hexadecane.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].C[O-].[Na+].Cl[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([CH2:23][C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)=[N:15][N:14]=1>O1CCOCC1>[OH:2][C:1]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[O:5][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([CH2:23][C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)=[N:15][N:14]=1
Reactant: Clc1nnc(Cc2ccncc2)c2ccccc12
Reactant: Oc1cccc(O)c1
Agent: C[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: Oc1cccc(Oc2nnc(Cc3ccncc3)c3ccccc23)c1
Temperature: 120 °C
Reaction time: 18 h

Procedure:
A solution of 0.2 g (1.82 mmol) resorcinol in 5 ml dioxane is spiked with 0.37 ml 5.4 M methanolic sodium methylate solution (2 mmol) The crystalline residue is then suspended in 5 ml dioxane, 0.511 g (2 mmol) 1-chloro-4-(4-pyridylmethyl)phthalazine is added, and the reaction mixture stirred under nitrogen atmosphere for 18 h at 120° C. After cooling to RT and filtration, the filtrate is evaporated under vacuum, and the residue purified by means of flash chromatography on silica gel with particle size 0.04-0.06 mm, using acetate and ethyl acetate/methanol mixtures (50:1 and 25:1). The product-containing fractions are evaporated under vacuum, the crystalline residue suspended in about 5 ml dichloromethane, and filtered. Title compound is obtained after drying of the crystallizate under HV (6 h, 100° C.); m.p. 206-207° C.; ESI-MS: (M+H)+=330.
Reaction SMILES: Cl[CH2:2][Si:3]([O:10][CH2:11][CH3:12])([O:7][CH2:8][CH3:9])[O:4][CH2:5][CH3:6].[C:13]([O-:18])(=[O:17])[C:14]([CH3:16])=[CH2:15].[K+]>C(P(CCCC)CCCC)CCC.C1C2NC3C(=CC=CC=3)SC=2C=CC=1>[C:13]([O:18][CH2:2][Si:3]([O:10][CH2:11][CH3:12])([O:7][CH2:8][CH3:9])[O:4][CH2:5][CH3:6])(=[O:17])[C:14]([CH3:16])=[CH2:15]
Reactant: C=C(C)C(=O)[O-]
Reactant: CCO[Si](CCl)(OCC)OCC
Agent: CCCCP(CCCC)CCCC
Agent: [K+]
Agent: c1ccc2c(c1)Nc1ccccc1S2
Product: C=C(C)C(=O)OC[Si](OCC)(OCC)OCC
Reaction time: 3 h
Yield: 93.3 %

Procedure:
Using a method analogous to Example 4, 212.7 g (1 mol) of chloromethyltriethoxysilane are reacted in the presence of 11.1 g (0.03 mol) of tri-n-butylphosphine and 0.1 g of phenothiazine with 130.4 g (1.05 mol) of potassium methacrylate at 90° C. The reaction is complete 3 hours after all the potassium methacrylate has been introduced. Work-up gives 244.7 g (93%) of methacryloxymethyltriethoxysilane having a purity of 99.2%.
Reaction SMILES: [CH2:1]([OH:4])[CH2:2][OH:3].[OH-].[K+].[C:7](#[N:10])[CH:8]=[CH2:9]>O>[CH2:8]([C:7]#[N:10])[CH2:9][O:3][CH2:2][CH2:1][O:4][CH2:9][CH2:8][C:7]#[N:10]
Reactant: C=CC#N
Reactant: OCCO
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: N#CCCOCCOCCC#N
Reaction time: 8 h

Procedure:
To a 5 liter double walled (for water cooling) glass reactor with a bottom drain and stopcock were charged 930 grams (15 moles) of ethylene glycol and 45.6 grams of 40% aqueous KOH solution. Some 1620 grams (30.0 moles) of acrylonitrile (NC--CH=CH2) were then added dropwise, with stirring, at such a rate that the temperature was kept below 35° C. After the addition was completed the mixture was stirred an additional hour and then allowed to stand overnight. The mixture was then neutralized to a pH of 7 by the addition of 6 molar HCL. After washing was saturated NaCl solution three times, the product was separated from the aqueous layer, dried over CaCl2 and passed through an Al2O3 column to insure that all basic materials had been removed. The yield obtained was 90% of theoretical.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.C(N(C(C)C)CC)(C)C.[O:18]=[C:19]([N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1)[CH2:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>C(O)CCC>[O:18]=[C:19]([N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1)[CH2:20][N:21]1[CH2:26][CH2:25][N:24]([C:2]2[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=2)[CH2:23][CH2:22]1
Reactant: O=C(CN1CCNCC1)N1CCCC1
Reactant: Nc1cc(Cl)ncn1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCO
Product: Nc1cc(N2CCN(CC(=O)N3CCCC3)CC2)ncn1
Temperature: 150 °C
Reaction time: 18 h

Procedure:
6-Chloropyrimidin-4-amine 7-2 (0.50 g, 3.86 mmol) and diisopropylethylamine (0.499 g, 3.86 mmol) were suspended in n-butanol and then 1-(2-oxo-2-pyrrolidin-1-ylethyl)piperazine 17-1 (0.762 g, 3.86 mmol) was added. The reaction was stirred at 150° C. for 18 hours and then the product was filtered off, washed with n-butanol and ethyl ether and air dried. 1H-NMR (CD3OD): 7.96 ppm (s, 1H); 5.72 ppm (s, 1H); 3.55 ppm (m, 6H); 3.44 ppm (t, 2H); 3.24 ppm (s, 2H); 2.60 ppm (t, 2H); 1.98 ppm (m, 2H); 1.88 ppm (m, 2H).
Reaction SMILES: [NH2:1][C:2]1[C:14]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[CH:13][C:5]2[N:6]=[C:7]([C:9]([CH3:12])([CH3:11])[CH3:10])[S:8][C:4]=2[CH:3]=1.C(=O)(O)[O-].[Na+].[C:26](Cl)(Cl)=[S:27]>C(Cl)(Cl)Cl.CCCCCC>[C:9]([C:7]1[S:8][C:4]2[CH:3]=[C:2]([N:1]=[C:26]=[S:27])[C:14]([N:15]3[CH2:16][CH2:17][O:18][CH2:19][CH2:20]3)=[CH:13][C:5]=2[N:6]=1)([CH3:12])([CH3:11])[CH3:10]
Reactant: S=C(Cl)Cl
Reactant: CC(C)(C)c1nc2cc(N3CCOCC3)c(N)cc2s1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCCCCC
Solvent: ClC(Cl)Cl
Product: CC(C)(C)c1nc2cc(N3CCOCC3)c(N=C=S)cc2s1
Reaction time: 10 h

Procedure:
To a cooled mixture of 143 g of 6-amino-2-tert-butyl-5-morpholinobenzothiazole and 168 g of sodium bicarbonate in 200 ml of CHCl3 is added 75 g of thiophosgene under stirring. The stirring is continued at ambient temperature for 10 hours. The solide are filtered off and the filtrate is evaporated. The solid thus obtained is dissolved in hexane and filtered through a silica gel column. The filtrate is evaporated to give 2-tert-butyl-6-isothiocyanato-5-[morpholin-4-yl]benzothiazole melting at 141°-143°.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]([OH:33])[C:10]([NH:13]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)=[N:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[CH2:45]Br>C1COCC1.ClCCl>[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[CH2:45][O:33][C:9]1[C:10]([NH2:13])=[N:11][CH:12]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:8]=1
Reactant: Oc1cc(-c2ccccc2)cnc1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: COc1cccc(CBr)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: COc1cccc(COc2cc(-c3ccccc3)cnc2N)c1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 59.2 %

Procedure:
To a solution of 5-phenyl-2-(trityl-amino)-pyridin-3-ol (100 mg, 0.24 mmol) in THF (3 mL) was added Cs2CO3 (79 mg, 0.24 mmol). The mixture was stirred at room temperature for 20 minutes, and then 3-methoxybenzylbromide (0.037 mL, 0.26 mmol) was added. The reaction was stirred at room temperature overnight, diluted with dichloromethane (5 mL), and filtered to remove the salts. The solvents were evaporated, and the residue was dissolved in 10% trifluoroacetic acid in dichloromethane (2 mL). The reaction was stirred for 2 hr, and evaporated. The residue was dissolved in dichloromethane, washed by sat. NaHCO3, and dried over Na2SO4. After filtration and concentration, the crude product was purified on a silica gel column eluting with methanol-dichloromethane (from 3% to 15% gradient) to provide 3-(3-methoxy-benzyloxy)-5-phenyl-pyridin-2-ylamine as a white solid (43.5 mg, 60% yield).
Reaction SMILES: [CH3:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[CH:5]=[C:4]([N:11]=[C:12]2[S:16][CH2:15][C:14]3([CH2:20][CH2:19][CH2:18][CH2:17]3)[NH:13]2)[N:3]=1.[CH2:21](Br)[CH:22]([CH3:24])[CH3:23].[H-].[Na+].CO>CN(C=O)C>[CH3:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[CH:5]=[C:4]([N:11]=[C:12]2[S:16][CH2:15][C:14]3([CH2:20][CH2:19][CH2:18][CH2:17]3)[N:13]2[CH2:21][CH:22]([CH3:24])[CH3:23])[N:3]=1
Reactant: CC(C)CBr
Reactant: Cc1cc(N=C2NC3(CCCC3)CS2)nc(C)c1C#N
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: CN(C)C=O
Product: Cc1cc(N=C2SCC3(CCCC3)N2CC(C)C)nc(C)c1C#N
Temperature: 50 °C
Yield: 17 %

Procedure:
To a solution of 2-(2,4-dimethyl-3-cyano-6-pyridylimino)-3-thia-1-azaspiro[4.4]nonane (Method C1e; 0.192 g, 0.669 mmol) and isobutyl bromide (0.5 mL) in anh. DMF (0.5 mL) was added NaH (95%; 0.62 g, 6.69 mmol) portionwise. The resulting mixture was heated at 50° C. for 3 h, then treated with MeOH (approximately 0.5 mL) and concentrated under reduced pressure. The residue was purified by chromatography (SiO2, gradient from 20% EtOAc/hex to 100% CH2Cl2) to give 2-(2,4-dimethyl-3-cyano-6-pyridylimino)-1-isobutyl-3-thia-1-azaspiro[4.4]nonane (0.04 g, 17%): CI-MS m/z 343 ((M+H)+).