Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][N:2]1[C:7](=[O:8])[C:6]([C:9]2([CH3:12])[CH2:11][CH2:10]2)=[N:5][N:4]=[C:3]1[SH:13].[CH4:14].CI>[OH-].[Na+]>[NH2:1][N:2]1[C:7](=[O:8])[C:6]([C:9]2([CH3:12])[CH2:10][CH2:11]2)=[N:5][N:4]=[C:3]1[S:13][CH3:14]
Reactant: CC1(c2nnc(S)n(N)c2=O)CC1
Reactant: C
Agent: [Na+]
Agent: [OH-]
Solvent: CI
Product: CSc1nnc(C2(C)CC2)c(=O)n1N
Reaction time: 6 h
Yield: 82.3 %

Procedure:
198 grams of the compound obtained according to (b) were dissolved in 500 ml of 2 normal NaOH and treated with 500 ml of methane and 150 grams of methyl iodide. The mixture was stirred for 6 hours at 20° to 30° C. The crystals formed were filtered off with suction, washed and dried. There are obtained 174.5 grams of final product (dried in a vacuum at 40° C.), white crystals, M.P. 115° to 116° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.C(N(CC)CC)C.[C:19](Cl)(=[O:22])[CH:20]=[CH2:21]>C1(C)C=CC=CC=1>[C:19]([O:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2)(=[O:22])[CH:20]=[CH2:21]
Reactant: Oc1cccc2cccnc12
Reactant: C=CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: C=CC(=O)Oc1cccc2cccnc12
Reaction time: 8 h

Procedure:
8-Hydroxyquinoline (58.0 g: 0.40 mole) was dissolved in a mixture of toluene (500 ml) and triethylamine (41.4 g; 0.41 mole). Acrylyl chloride (38.0 g; 0.42 mole) was added slowly, while stirring, the reaction temperature beting kept under 30° C. When the addition was complete the mixture was stirred for another 1 hour. The solution was then filtered and washed with a solution of sodium hydrogen carbonate in water followed by water only, and finally the toluene layer was dried with anhydrous sodium sulphate. Some toluene was evaporated off using a rotary evaporator under low pressure. The solution was left in a refrigerator overnight and the solid formed was filtered off. This was identified by infra-red and N.M.R. spectroscopy and microanalysis to be 8-quinolinyl acrylate. Yield 48.6 g (61 percent of the theoretical yield).
Reaction SMILES: [CH2:1]([O:8][CH2:9][N:10]1[C:18]2[C:17](Cl)=[N:16][CH:15]=[N:14][C:13]=2[C:12]([CH2:20][N:21]([CH3:30])[C@@H:22]([C@H:25]([OH:29])[CH2:26][S:27][CH3:28])[CH2:23][OH:24])=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH3:31]>CO>[NH3:10].[NH2:31][C:17]1[C:18]2[N:10]([CH2:9][O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:11]=[C:12]([CH2:20][N:21]([CH3:30])[C@@H:22]([C@H:25]([OH:29])[CH2:26][S:27][CH3:28])[CH2:23][OH:24])[C:13]=2[N:14]=[CH:15][N:16]=1
Reactant: CSC[C@@H](O)[C@@H](CO)N(C)Cc1cn(COCc2ccccc2)c2c(Cl)ncnc12
Agent: N
Solvent: CO
Product: CSC[C@@H](O)[C@@H](CO)N(C)Cc1cn(COCc2ccccc2)c2c(N)ncnc12
Yield: 52 %

Procedure:
A solution of (2R,3S)-2-(((5-(benzyloxymethyl)-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)(methyl)amino)-4-(methylthio)butane-1,3-diol (240 mg, 0.5 mmol) in 7N NH3 in MeOH (5 ml) was heated in a sealed tube at 140 C (bath temp) overnight. The reaction was concentrated in vacuo and the resulting residue purified by flash chromatography on silica gel eluting with 10%. MeOH/DCM=>10% 7 N NH3 to afford (2R,3S)-2-(((4-amino-5-(benzyloxymethyl)-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)(methyl)amino)-4-(methylthio)butane-1,3-diol (120 mg, 52%) as a syrup. 1H NMR (CD3OD) δ 8.16 (s, 1H), 7.41 (s, 1H), 7.27 (m, 5H), 5.60 (s, 2H), 4.57 (s, 2H), 4.07 (d, J=15.0 Hz, 1H), 3.82 (m, 3H), 3.71 (dd, J=12.0, 6.0 Hz, 1H), 2.88 (m, 1H), 2.77 (dd, J=15.0, 3.0 Hz, 1H), 2.54 (dd, J=15.0, 6.0 Hz, 1H), 2.43 (s, 3H), 2.03 (s, 3H). 13C NMR (CD3OD) δ 153.2, 151.8, 150.4, 138.2, 134.4, 130.0, 129.7, 129.6, 116.8, 115.3, 79.0, 71.8, 70.8, 67.0, 60.2, 50.0, 40.2, 39.1, 16.8.
Reaction SMILES: CC1(C)[O:6][C:5](=[CH:7][C:8]([N:10]([CH2:13][C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=2)[O:11][CH3:12])=[O:9])[C:4](=O)[O:3]1.[CH3:25][S:26]([NH2:29])(=[O:28])=[O:27]>>[OH:6][C:5]([C:4]([NH:29][S:26]([CH3:25])(=[O:28])=[O:27])=[O:3])=[CH:7][C:8]([N:10]([CH2:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=1)[O:11][CH3:12])=[O:9]
Reactant: CS(N)(=O)=O
Reactant: CON(Cc1ccc(C(=O)O)cc1)C(=O)C=C1OC(C)(C)OC1=O
Product: CON(Cc1ccc(C(=O)O)cc1)C(=O)C=C(O)C(=O)NS(C)(=O)=O
Yield: 95.1 %

Procedure:
Reaction of 4-({[2-(2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetyl]-methoxy-amino}-methyl)-benzoic acid (0.125 g, 0.37 mmol) with methanesulfonamide (0.053 g, 0.55 mmol) as described for compound 1 gave 0.131 g (95%) of the title amide as a white solid after recrystallization from acetonitrile; mp 119-124° C. 1H NMR (400 MHz, DMSO) δ: (ppm)); mixture of rotamers: 2.99 and 3.09 (3H, 2 S, SO2CH3), 3.42 and 3.54 (3H, 2 s, OCH3), 4.63 and 4.76 (2H, 2 s, NCH2), 6.14 (1H, s, CH), 7.17 (2H, m, aromatics), 7.69 (2H, m, aromatics). HRMS (ESI/pos) calculated for C14H17N2O8S, [M+H]+: 373.070563; found: 373.070061. Anal. calcd for C14H16N2O8S: C, 45.16; H, 4.33; N, 7.52; found: C, 45.22; H, 4.70; N, 8.12.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[C:11]#[N:12].S(Cl)(Cl)=O.[NH2:17][C:18]1[C:19]([Cl:24])=[N:20][CH:21]=[N:22][CH:23]=1.N1C=CC=CC=1>C1C=CC=CC=1.O.C(Cl)(Cl)Cl.ClCCl>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:17][C:18]2[C:19]([Cl:24])=[N:20][CH:21]=[N:22][CH:23]=2)=[O:8])=[CH:4][C:3]=1[C:11]#[N:12]
Reactant: Nc1cncnc1Cl
Reactant: N#Cc1cc(C(=O)O)ccc1Cl
Solvent: O
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: N#Cc1cc(C(=O)Nc2cncnc2Cl)ccc1Cl
Temperature: 25 °C
Reaction time: 7 h
Yield: 65 %

Procedure:
4-Chloro-3-cyanobenzoic acid (7.01 g, 38.6 mmol) was suspended in benzene (70 mL). Thionyl chloride (3.6 mL, 49.6 mmol) was added to the suspension, and the mixture was refluxed with heating for 4 hours. The reaction liquid was condensed under reduced pressure. 5-Amino-4-chloropyrimidine (5.00 g, 38.6 mmol), dichloromethane (70 mL), and pyridine (3.6 mL, 44.5 mmol) were added to the obtained acid chloride. The mixture was stirred at room temperature for 7 hours. Chloroform (50 mL) and water (50 mL) was added to the reaction solution to filtrate crystals. The obtained crystals were washed with chloroform (20 mL) and water (20 mL), and air-dried to obtain 7.35 g (yield: 65%) of the subject compound as white crystals. Further, 0.62 g (yield: 8%) of the subject compound was obtained from a mixed solution of mother liquid and washings as pale brown crystals (secondary crystals). The total yield was 73%.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[CH:17]=[CH:16][C:15]([NH2:18])=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[C:19]([O:23][C:24]([C:26]1[CH:27]=[C:28]([C:32]2[O:36][CH:35]=[N:34][C:33]=2[C:37](O)=[O:38])[CH:29]=[CH:30][CH:31]=1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>>[C:19]([O:23][C:24](=[O:25])[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]2[O:36][CH:35]=[N:34][C:33]=2[C:37](=[O:38])[NH:18][C:15]2[CH:16]=[CH:17][N:13]([CH2:12][C:10]3[O:11][C:7]([C:2](=[O:6])[CH3:1])=[CH:8][CH:9]=3)[N:14]=2)[CH:27]=1)([CH3:22])([CH3:20])[CH3:21]
Reactant: CC(C)(C)OC(=O)c1cccc(-c2ocnc2C(=O)O)c1
Reactant: CC1(c2ccc(Cn3ccc(N)n3)o2)OCCO1
Product: CC(=O)c1ccc(Cn2ccc(NC(=O)c3ncoc3-c3cccc(C(=O)OC(C)(C)C)c3)n2)o1

Procedure:
Following general procedure B followed by C, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-1H-pyrazol-3-ylamine and 5-(3-tert-butoxycarbonyl-phenyl)-oxazole-4-carboxylic acid. LC-MS-conditions 02: tR=1.09 min; [M+H]+=477.45.
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:11]1[C:19]2[C:14](=[CH:15][C:16]([C:20]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[O:21])=[CH:17][CH:18]=2)[NH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[F:10].O=[CH:29][C:30]([O:32][CH2:33][CH3:34])=[O:31].C1(C)C=CC=CC=1.Cl.O1CCOCC1>O1CCOCC1.C1(C)C=CC=CC=1.[Pd]>[F:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[C:3]1[C:11]2[C:19]3[C:14](=[CH:15][C:16]([C:20]([N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)=[O:21])=[CH:17][CH:18]=3)[NH:13][C:12]=2[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[N:1][CH:2]=1
Reactant: CCOC(=O)C=O
Reactant: NCC(c1ccccc1F)c1c[nH]c2cc(C(=O)N3CCOCC3)ccc12
Agent: [Pd]
Agent: Cl
Solvent: C1COCCO1
Solvent: Cc1ccccc1
Product: CCOC(=O)c1ncc(-c2ccccc2F)c2c1[nH]c1cc(C(=O)N3CCOCC3)ccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 17.9 %

Procedure:
To a yellow, homogeneous solution of (3-(2-amino-1-(2-fluorophenyl)ethyl)-1H-indol-6-yl)(morpholino)methanone (0.270 g, 0.736 mmol) and 50% ethyl 2-oxoacetate/toluene (0.321 mL, 1.619 mmol) in 1,4-dioxane (30 mL) was added 4 N HCl/dioxane (0.368 mL, 1.472 mmol) under nitrogen, and the reaction was stirred overnight. The reaction was concentrated in vacuo, diluted with water and basified to pH ˜10 (by litmus paper) with NaHCO3. This was extracted with EtOAc (3×), and the organic layers were combined and washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give crude product which was used in the subsequent step. This was combined with 10% Pd/C (0.710 g, 0.668 mmol) in toluene (10 mL), and the solution was refluxed. After 45 min, the reaction was cooled to room temperature and filtered through a pad of CELITE®, rinsing with EtOAc. The filtrate was washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give a residue which was purified by flash chromatography using an ISCO 24 g column eluting with 0-100% EtOAc/hexanes. Appropriate fractions were collected and concentrated in vacuo to give the desired product (0.0592 g, 0.132 mmol, 19.8% yield) as an off-white solid.
Reaction SMILES: [OH:1][CH2:2][C:3]([CH3:40])([CH3:39])[O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:16](=[O:17])[C:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=4)=[CH:21][CH:20]=3)=[C:14]([CH2:33][CH2:34][CH3:35])[N:13]3[N:36]=[CH:37][N:38]=[C:12]23)=[CH:7][CH:6]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O.C(OCC)(=O)C.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl.O>[CH3:40][C:3]([CH3:39])([O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:16](=[O:17])[C:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=4)=[CH:21][CH:20]=3)=[C:14]([CH2:33][CH2:34][CH3:35])[N:13]3[N:36]=[CH:37][N:38]=[C:12]23)=[CH:7][CH:6]=1)[CH:2]=[O:1]
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(-c2ccc(OC(C)(C)CO)cc2)c2ncnn12
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(-c2ccc(OC(C)(C)C=O)cc2)c2ncnn12
Reaction time: 3 h
Yield: 100.4 %

Procedure:
To a solution of 4′-({4-[4-(2-hydroxy-1,1-dimethylethoxy)phenyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.97 g) in methylene chloride (10 mL) was added 1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one (2.3 g), and the mixture was stirred for 3 hr. Ethyl acetate, water and sodium thiosulfate were added to the reaction mixture, and the mixture was stirred for 30 min, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.97 g, 99%).
Reaction SMILES: Cl.[CH2:2]1[O:31][C:30]2[C:4](=[CH:5][C:6]3[O:11][CH2:10][C@H:9]([CH2:12][NH:13][CH2:14][CH2:15][CH2:16][O:17][C:18]4[CH:28]=[CH:27][C:21]5[CH:22]=[CH:23][C:24](=[O:26])[O:25][C:20]=5[CH:19]=4)[O:8][C:7]=3[CH:29]=2)[O:3]1.I[CH2:33][CH3:34].C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH2:2]1[O:31][C:30]2[C:4](=[CH:5][C:6]3[O:11][CH2:10][C@H:9]([CH2:12][N:13]([CH2:33][CH3:34])[CH2:14][CH2:15][CH2:16][O:17][C:18]4[CH:28]=[CH:27][C:21]5[CH:22]=[CH:23][C:24](=[O:26])[O:25][C:20]=5[CH:19]=4)[O:8][C:7]=3[CH:29]=2)[O:3]1
Reactant: O=c1ccc2ccc(OCCCNC[C@H]3COc4cc5c(cc4O3)OCO5)cc2o1
Reactant: CCI
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCN(CCCOc1ccc2ccc(=O)oc2c1)C[C@H]1COc2cc3c(cc2O1)OCO3
Temperature: 60 °C
Yield: 43.8 %

Procedure:
(S)-7-[3-[[(2,3-Dihydro-6,7-methylenedioxy-1,4-benzodioxin-2-yl)methyl]amino]propoxy]-2H-1-benzopyran-2-one hydrochloride (0.60 g, 1.3 mmole), iodoethane (0.16 ml, 2.0 mmole) and diisopropylethylamine (2.26 ml, 13.0 mmole) were combined in 50 ml of DMF and heated at 60° C. for 2 days under a nitrogen atmosphere. The solvent was then removed in vacuum and the residue was dissolved in dichloromethane and washed with an equal volume of aqueous saturated sodium bicarbonate. The aqueous portion was back-extracted with dichloromethane and the combined organic portions were washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column using dichloromethane as eluant. The product-containing fractions were combined and concentrated in vacuum, and the residue redissolved in methanol and acidified with 4N HCl/isopropanol to pH<3 in an ice bath. The mixture was diluted with isopropanol to precipitate a white solid, which was recrystallized from methanol to give 0.25 g of the title compound as the monohydrochloride, m.p. 209° C.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:26])/[CH:11]=[CH:12]/[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)[CH:14]=2)=[CH:5][CH:4]=1.Cl.Cl.[CH3:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([N:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)=[CH:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH3:29][O:30][C:31]1[CH:32]=[CH:33][C:34]([N:37]2[CH2:42][CH2:41][N:40]([CH2:2][C:3]3[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:26])/[CH:11]=[CH:12]/[C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([C:19]5[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=5)[CH:14]=4)=[CH:5][CH:4]=3)[CH2:39][CH2:38]2)=[CH:35][CH:36]=1
Reactant: COc1ccc(N2CCNCC2)cc1
Reactant: Cc1ccc(-c2cccc(/C=C/C(=O)Nc3ccc(CCl)cc3)c2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(N2CCN(Cc3ccc(NC(=O)/C=C/c4cccc(-c5ccc(C)cc5)c4)cc3)CC2)cc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 78.3 %

Procedure:
In DMF (3ml) was dissolved (E)-N-[4-(chloromethyl)-phenyl]-3-(4-methylphenyl)cinnamamide (200mg), and to the solution were added 1-(4-methoxyphenyl)piperazine dihydrochloride (190mg) and potassium carbonate (382mg). The mixture was stirred at room temperature for 14 hours, and to the mixture was added water (50ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-diisopropylether to give (E)-N-[4-[1-(4-methoxy-phenyl)-4-piperazinylmethyl]phenyl]-3-(4-methylphenyl)-cinnamamide (Compound 62) (224mg) as colorless crystals.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([O:11][CH3:12])[CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[Li]CCCC.[C:18](=[O:20])=[O:19]>C1COCC1.CCCCCC>[CH3:12][O:11][C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([C:18]([OH:20])=[O:19])[CH:3]=1)[NH:9][CH:8]=[CH:7]2
Reactant: COc1cc(Br)c2[nH]ccc2c1
Reactant: O=C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: COc1cc(C(=O)O)c2[nH]ccc2c1

Procedure:
A solution of 7-Bromo-5-methoxy-1H-indole (described in WO 2002028861) in THF was treated with 2 eq. of a solution of n-BuLi in n-hexane (1.6M) at 5° and after 30 min at this temperature was cooled to −75°. Dry ice (excess) was added and after 15 mins the mixture was quenched with H2O and washed with EtOAc. After acidification of the aqueous layer and extraction into CH2Cl2, evaporation gave the desired product.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][S:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1)(=[O:8])=[O:7].[CH2:16]([NH:18][CH:19]([CH3:21])[CH3:20])[CH3:17].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:16]([N:18]([CH:19]([CH3:21])[CH3:20])[CH2:2][CH2:3][CH2:4][S:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1)(=[O:8])=[O:7])[CH3:17]
Reactant: CCNC(C)C
Reactant: Cc1ccc(S(=O)(=O)SCCCCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCN(CCCSS(=O)(=O)c1ccc(C)cc1)C(C)C

Procedure:
Toluene-4-thiosulfonic acid S-(3-chloro-propyl) ester (12.0 g, 45.3 mol, 1.00 eq.), N-ethylisopropylamine (4.2 g, 48.0 mmol, 1.05 eq.) and potassium carbonate (6.9 g, 49.9 mmol, 1.10 eq.) were stirred together in acetonitrile (160 mL) at 60° C. for 18 hours. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate (500 mL) and water (250 mL). The organic solution was washed with brine (250 mL), dried (MgSO4) and the resulting oil was purified by MPLC chromatography to give an oil weighing 2.98 g (21%).
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([C:14]2[CH:18]=[C:17]([CH2:19][CH2:20][CH:21]=O)[O:16][N:15]=2)[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:23][C:24]([F:39])([F:38])[C:25]1[CH:37]=[CH:36][CH:35]=[CH:34][C:26]=1[CH2:27][N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[O:1]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]2[CH:18]=[C:17]([CH2:19][CH2:20][CH2:21][N:31]3[CH2:30][CH2:29][N:28]([CH2:27][C:26]4[CH:34]=[CH:35][CH:36]=[CH:37][C:25]=4[C:24]([F:38])([F:39])[F:23])[CH2:33][CH2:32]3)[O:16][N:15]=2)[CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=CCCc1cc(-c2cccc(Oc3ccccc3)c2)no1
Reactant: FC(F)(F)c1ccccc1CN1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: FC(F)(F)c1ccccc1CN1CCN(CCCc2cc(-c3cccc(Oc4ccccc4)c3)no2)CC1
Yield: 93.9 %

Procedure:
About 2 min after dissolving 3-[3-(3-phenoxyphenyl)isoxazol-5-yl]propanal (10 mg, 0.03 mmol) and 1-[2-(trifluoromethyl)benzyl]piperazine (7.1, 0.03 mmol) in 2 mL of dry methylene chloride, were added NaBH(OAc)3 (22 mg, 0.10 mmol) and molecular sieves (5 beads). The reaction mixture was reacted for 4 hr and followed the same processes as in Example 1 to obtain 14.7 mg (82.7%) of the target compound.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14].[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1>C(#N)C>[N:15]1([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1
Reactant: OCCCCCCCCCCCCBr
Reactant: C1COCCN1
Solvent: CC#N
Product: OCCCCCCCCCCCCN1CCOCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.4 %

Procedure:
To a solution of 5.30 g (20 mmol) of 12-bromo-1-dodecanol in 100 ml of acetonitrile is added dropwise 6 ml (68.6 mmol) of morpholine at 0° C. The solution is then stirred at room temperature overnight and filtered. After removal of the acetonitrile, the residue is dissolved in 250 ml of dichloromethane. The dichloromethane solution is washed with water, dried over magnesium sulfate and filtered. The dichloromethane is removed under reduced pressure and the residue is purified by silica gel column chromatography to give 4.2 g (79.2%) of 12-(4-morpholinyl)-1-dodecanol.
Reaction SMILES: [CH2:1]1[O:17][C:16]2[C:3](=[CH:4][C:5]3[CH:6]=[C:7]([CH2:26][N:27]4[CH2:34][CH2:33][CH2:32][C@H:28]4[C:29]([OH:31])=[O:30])[C:8]4[C:13]([C:14]=3[CH:15]=2)=[CH:12][C:11]([O:18]CC2C=CC=CC=2)=[CH:10][CH:9]=4)[O:2]1.N>>[CH2:1]1[O:17][C:16]2[C:3](=[CH:4][C:5]3[CH:6]=[C:7]([CH2:26][N:27]4[CH2:34][CH2:33][CH2:32][C@H:28]4[C:29]([OH:31])=[O:30])[C:8]4[C:13]([C:14]=3[CH:15]=2)=[CH:12][C:11]([OH:18])=[CH:10][CH:9]=4)[O:2]1
Reactant: O=C(O)[C@@H]1CCCN1Cc1cc2cc3c(cc2c2cc(OCc4ccccc4)ccc12)OCO3
Agent: N
Product: O=C(O)[C@@H]1CCCN1Cc1cc2cc3c(cc2c2cc(O)ccc12)OCO3

Procedure:
General procedure g from 18 (95%); white powder; mp 205-206° C.; 1H NMR (400.13 MHz) δ 8.07 (d, J=4 Hz, 1H), 7.82 (s, 1H), 7.80 (d, J=2 Hz, 1H), 7.42 (s, 1H), 7.21 (dd, J=4 Hz, 2 Hz, 1H), 7.10 (s, 1H), 6.04 (s, 2H), 4.09 (s, 2H), 3.16 (m, 1H), 2.38 (m, 2H), 2.23 (m, 2H), 1.95 (m, 2H); MS (DCI/NH3) m/e: 366 (M+H)+.
Reaction SMILES: C(OC(COC(=O)C)C=C)(=O)C.[H][H].[C]=O.[C:17]([O:20][CH2:21][CH:22](OC(=O)C)[CH:23]([CH:25]=[O:26])[CH3:24])(=[O:19])[CH3:18].C(OC(COC(=O)C)CCC=O)(=O)C>C1(C)C=CC=CC=1.C/C(/O)=C/C(C)=O.[C-]#[O+].[C-]#[O+].[Rh].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(O)(=O)C>[C:17]([O:20][CH2:21][CH:22]=[C:23]([CH3:24])[CH:25]=[O:26])(=[O:19])[CH3:18]
Reactant: [H][H]
Reactant: CC(=O)OCC(OC(C)=O)C(C)C=O
Agent: [Rh]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: C=CC(COC(C)=O)OC(C)=O
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Product: CC(=O)OCC=C(C)C=O
Temperature: 80 °C
Reaction time: 2 h
Yield: 37.3 %

Procedure:
An autoclave equipped with a gas inlet, a sampling port and an electromagnetic stirrer and having an internal volume of 300 ml, was charged with 50 ml (52.7 g, 0.306 mol) of 3,4-diacetoxy-1-butene and a solution of 2.58 mg of rhodium dicarbonyl acetylacetonate and 140 mg (0.5 mmol) of tricyclohexylphosphine in 50 ml of toluene under nitrogen while avoiding their contact with air. Then, the atmosphere inside the autoclave was replaced with a gaseous mixture of hydrogen and carbon monoxide at a molar ratio of 1/1. The pressure inside the autoclave was adjusted to 90 atmospheric pressure (gauze pressure) with the same gaseous mixture and the temperature inside the autoclave was raised to 80° C. The hydroformylation was effected for 2 hours at 80° C. while maintaining the pressure inside the autoclave at 90 atmospheric pressure (gauze pressure) with the gaseous mixture of hydrogen and carbon monoxide at a molar ratio of 1/1. Analysis of the reaction solution with gas chromatography under the same conditions of Example 1 showed that the conversion of the 3,4-diacetoxy-1-butene was 44% and the selectivity to the hydroformylated product was 99%. The anaysis also showed that the reaction solution contained 13.55 g (67 mmol) of 1,2-diacetoxy-3-formylbutane and 8.29 g (41 mmol) of 4,5-diacetoxypentanal and 3.55 g (25 mmol) of 3-methyl-4-oxo-2-butenyl acetate which was formed by the elimination of acetic acid from 1,2-diacetoxy-3-formylbutane. The ratio i/n was 2.2 (=69/31), wherein 3-methyl-oxo-2-butenyl acetate was calculated as 1,2-diacetoxy-3-formylbutane.
Reaction SMILES: [Br:1][C:2]1[C:3]([NH:9][CH3:10])=[N:4][C:5](Cl)=[N:6][CH:7]=1.[CH3:11][N:12]1[C:16]([CH3:17])=[C:15]([NH2:18])[CH:14]=[N:13]1.C(O)(C(F)(F)F)=O>COCCO>[Br:1][C:2]1[C:3]([NH:9][CH3:10])=[N:4][C:5]([NH:18][C:15]2[CH:14]=[N:13][N:12]([CH3:11])[C:16]=2[CH3:17])=[N:6][CH:7]=1
Reactant: Cc1c(N)cnn1C
Reactant: CNc1nc(Cl)ncc1Br
Solvent: COCCO
Solvent: O=C(O)C(F)(F)F
Product: CNc1nc(Nc2cnn(C)c2C)ncc1Br
Temperature: 100 °C
Reaction time: 1.5 h
Yield: 17.1 %

Procedure:
To a mixture of 5-bromo-2-chloro-N-methylpyrimidin-4-amine (0.201 g, 0.903 mmol) and 1,5-dimethyl-1H-pyrazol-4-amine (0.12 g, 1.08 mmol) in 2-methoxyethanol (2 mL) was added TFA (0.070 mL, 0.9 mmol). The reaction was stirred in a sealed tube at 100° C. for 90 minutes. The resulting precipitate was collected by filtration. The isolated solid was further purified by reverse phase HPLC to give 5-bromo-N2-(1,5-dimethyl-1H-pyrazol-4-yl)-N4-methylpyrimidine-2,4-diamine (46 mg, 17%). LCMS (Method A): [MH+]=297.0 at 2.57 min. 1H-NMR (DMSO): δ 8.28 (s, 1H), 7.84 (s, 1H), 7.49 (s, 1H), 6.79 (d, J=3.4, 1H), 3.67 (s, 3H), 2.82 (d, J=3.6, 3H), 2.14 (s, 3H). Ki=0.017 μM.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:11][C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[N:15][C:16]([Cl:22])=[CH:17][CH:18]=2)[N:13]=1.C(O)CC>O>[Cl:22][C:16]1[N:15]=[C:14]2[C:19]([CH:20]=[CH:21][C:12]([NH:11][C:4](=[O:6])[C:3]3[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=3[F:1])=[N:13]2)=[CH:18][CH:17]=1
Reactant: Nc1ccc2ccc(Cl)nc2n1
Reactant: O=C(O)c1ccccc1F
Solvent: CCCO
Solvent: O
Product: O=C(Nc1ccc2ccc(Cl)nc2n1)c1ccccc1F
Temperature: 4 °C
Yield: 55.5 %

Procedure:
The procedure is similar to that described in Example 1, but starting with 2-fluorobenzoic acid (11.2 g), N,N'-carbonyldiimidazole (12.9 g) and 2-amino-7-chloro-1,8-naphthyridine (8.9 g). The product produced by precipitation in water (13.6 g; m.p. 218° C.) is dissolved in boiling 1-propanol (450 cc). After 3 hours' cooling at 4° C., the crystallised solid is separated by filtration, washed with 1-propanol (3×20 cc) and dried at 40° C. under reduced pressure (0.067 kPa). N-(7-chloro-1,8-naphthyridin-2-yl)-2-fluorobenzamide (8.3 g) is produced, m.p. 222° C. EXAMPLE 14