Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6]2)#[N:2].[BH4-].[Na+]>CO.C(Cl)Cl>[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH:8]([OH:12])[CH2:7][CH2:6]2)#[N:2]
Reactant: N#Cc1ccc2c(c1)CCC2=O
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: N#Cc1ccc2c(c1)CCC2O
Reaction time: 3 h
Yield: 71.2 %

Procedure:
A solution of 5-cyano-1-indanone (3.40 g, 21.63 mmol, prepared according to Reich, S. H., et. al. J. Med. Chem., 2000, 43, 1670–1683) in methanol (50 mL) was treated with sodium borohydride (0.25 g, 6.48 mmol). After stirring for 3 h, the reaction was diluted with methylene chloride (50 mL) and washed with saturated aqueous sodium bicarbonate (50 mL). The aqueous layer was further extracted with methylene chloride (2 50 mL). The extracts were combined, dried over magnesium sulfate and concentrated in vacuo. Silica gel chromatography eluting with 40% ethyl acetate/hexanes gave 2.45 g (15.40 mmol, 71%) of the title compound as a white solid: 1H NMR (500 MHz, CDCl3) δ 7.48–7.54 (m, 3H), 5.25–5.29 (m, 1H), 3.03–3.10 (m, 2H), 2.81–2.89 (m, 2H), 2.52–2.59 (m, 2H), 1.94–2.01 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ 150.1, 144.2, 130.9, 128.6, 125.0, 119.1, 111.8, 75.9, 35.8, 29.5.
Reaction SMILES: [Cl:1][C:2]1[C:7](S)=[C:6]([Cl:9])[C:5]([Cl:10])=[C:4]([Cl:11])[C:3]=1[Cl:12].[N+:13]([O-])([OH:15])=[O:14].ClC1C(Cl)=C(Cl)C(Cl)=C(Cl)C=1Cl>OS(O)(=O)=O.O=S(=O)=O>[C:7]1([N+:13]([O-:15])=[O:14])[C:2]([Cl:1])=[C:3]([Cl:12])[C:4]([Cl:11])=[C:5]([Cl:10])[C:6]=1[Cl:9]
Reactant: O=[N+]([O-])O
Reactant: Sc1c(Cl)c(Cl)c(Cl)c(Cl)c1Cl
Agent: Clc1c(Cl)c(Cl)c(Cl)c(Cl)c1Cl
Agent: O=S(=O)(O)O
Agent: O=S(=O)=O
Product: O=[N+]([O-])c1c(Cl)c(Cl)c(Cl)c(Cl)c1Cl
Temperature: 25 °C
Reaction time: 16 h
Yield: 73.5 %

Procedure:
Pentachlorothiophenol (10.0 g, 0.035 mol) was added to 60.0 g of 70% nitric acid at room temperature. The reaction mixture was heated at reflux 7 hr followed by stirring at room temperature 16 hr. At this point, 40 mL of 30% oleum (30% by weight sulfur trioxide in sulfuric acid) was added at such a rate that the temperature was maintained between 55° and 60° C. After the addition was complete (30 min), the reaction mixture was heated at 108° C. for 30 minutes. The reaction mixture was then cooled to room temperature, filtered, the product washed with water and dried in vacuo to give 7.6 g (74% yield) of 99.0% PCNB with 1.0% hexachlorobenzene (GC assay).
Reaction SMILES: C([O:8][CH2:9][C@@H:10]1[CH2:15][N:14]([CH3:16])[CH2:13][CH2:12][N:11]1[C:17]1[CH:18]=[CH:19][C:20]([O:41][C:42]([F:45])([F:44])[F:43])=[C:21]([NH:23][C:24]2[N:33]=[CH:32][C:31]3[CH2:30][CH2:29][C:28]4[C:34]([C:38]([NH2:40])=[O:39])=[N:35][N:36]([CH3:37])[C:27]=4[C:26]=3[N:25]=2)[CH:22]=1)C1C=CC=CC=1.B(Cl)(Cl)Cl.CO>C(Cl)Cl>[OH:8][CH2:9][C@@H:10]1[CH2:15][N:14]([CH3:16])[CH2:13][CH2:12][N:11]1[C:17]1[CH:18]=[CH:19][C:20]([O:41][C:42]([F:43])([F:44])[F:45])=[C:21]([NH:23][C:24]2[N:33]=[CH:32][C:31]3[CH2:30][CH2:29][C:28]4[C:34]([C:38]([NH2:40])=[O:39])=[N:35][N:36]([CH3:37])[C:27]=4[C:26]=3[N:25]=2)[CH:22]=1
Reactant: CN1CCN(c2ccc(OC(F)(F)F)c(Nc3ncc4c(n3)-c3c(c(C(N)=O)nn3C)CC4)c2)[C@H](COCc2ccccc2)C1
Agent: ClB(Cl)Cl
Solvent: CO
Solvent: ClCCl
Product: CN1CCN(c2ccc(OC(F)(F)F)c(Nc3ncc4c(n3)-c3c(c(C(N)=O)nn3C)CC4)c2)[C@H](CO)C1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
To a solution of 8-[5-((S)-2-benzyloxymethyl-4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (53 mg, 0.08 mmol) in DCM (1.7 mL) under an atmosphere of N2, at −78° C. 1M BCl3 in DCM (0.17 mL) was added dropwise. Under complete addition the solution was stirred at 0° C. for 30 min and at room temperature overnight. Then 2 mL of MeOH was added. The solvent was removed under reduced pressure and the residue was diluted with Et2O and decanted to give the desired compound in quantitative yield (46 mg) as a brown solid.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]2[N:8]([C@H:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH3:13])[C:9]([OH:11])=[N:10][C:5]2=[N:4][CH:3]=1.[CH:20](B(O)O)=[CH2:21]>>[C:14]1([C@@H:12]([N:8]2[C:6]3=[N:7][C:2]([CH:20]=[CH2:21])=[CH:3][N:4]=[C:5]3[N:10]=[C:9]2[OH:11])[CH3:13])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: C=CB(O)O
Reactant: C[C@@H](c1ccccc1)n1c(O)nc2ncc(Br)nc21
Product: C=Cc1cnc2nc(O)n([C@@H](C)c3ccccc3)c2n1
Temperature: 90 °C
Yield: 54 %

Procedure:
A scintillation vial equipped with a stirbar was charged with (S)-6-bromo-1-(1-phenylethyl)-1H-imidazo[4,5-b]pyrazin-2-ol (1.0 equiv), vinyl boronic acid (2.2 equiv), and (DPPF)PdCl2 (0.10 equiv). The vial was fitted with a septum-lined cap and purged with nitrogen for 5-10 min. To this mixture was added dioxane (16.6 volume equivalents) and degassed 2 N K2CO3 (4.2 volume equivalents) by syringe. The resulting mixture was heated to 90° C. overnight. The mixture was cooled to room temperature, diluted with 12 volume equivalents EtOAc, washed with twice with saturated aq. NaHCO3, and once with brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Biotage MPLC 5%-40% EtOAc/Hexanes) provided the title compound as an off-white solid (54%). LCMS m/z (APCI)=267.0 (M+H).
Reaction SMILES: [OH:1][C:2]([C:5]1[C:6]2[N:7]([C:11]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH:21]4[CH2:26][CH2:25][CH:24]([C:27](O)=[O:28])[CH2:23][CH2:22]4)[N:15]=3)=[CH:12][N:13]=2)[CH:8]=[CH:9][CH:10]=1)([CH3:4])[CH3:3].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.[NH:66]1[CH2:71][CH2:70][CH:69]([OH:72])[CH2:68][CH2:67]1>CN(C=O)C>[OH:1][C:2]([C:5]1[C:6]2[N:7]([C:11]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH:21]4[CH2:26][CH2:25][CH:24]([C:27]([N:66]5[CH2:71][CH2:70][CH:69]([OH:72])[CH2:68][CH2:67]5)=[O:28])[CH2:23][CH2:22]4)[N:15]=3)=[CH:12][N:13]=2)[CH:8]=[CH:9][CH:10]=1)([CH3:3])[CH3:4]
Reactant: CC(C)(O)c1cccn2c(-c3ccnc(NC4CCC(C(=O)O)CC4)n3)cnc12
Reactant: OC1CCNCC1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(O)c1cccn2c(-c3ccnc(NC4CCC(C(=O)N5CCC(O)CC5)CC4)n3)cnc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.3 %

Procedure:
A mixture of 4-{4-[8-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid (0.175 g), BOP (0.39 g), DIEA (0.23 mL), and piperidin-4-ol (67 mg) in DMF (5 mL) was stirred at RT overnight. The resulting solid was filtered and dried, purified by ISCO using 100% DCM to 20% MeOH/DCM. The fractions were collected and concentrated, then titurated with EtOAc, and the resulting solid filtered and dried at 50° C. overnight to provide (4-{4-[8-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-(4-hydroxy-piperidin-1-yl)-methanone (Compound 2, 140.4 mg). Mp=188.0-190.0° C.
Reaction SMILES: N([O-])=O.[Na+].[CH:5]1[C:14]2[C:9](=[C:10](N)[CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][N:6]=1.[BrH:16].[NH4+]>O>[Br:16][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:9]=1[CH:8]=[CH:7][N:6]=[CH:5]2
Reactant: Br
Reactant: Nc1cccc2cnccc12
Agent: O=N[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: O
Product: Brc1cccc2cnccc12
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 53.1 %

Procedure:
A solution of sodium nitrite (2.15 g, 31.21 mmol) in water (2 mL) was added to a solution of isoquinolin-5-ylamine (3.0 g, 20.80 mmol) in aqueous 46% hydrogen bromide (9.98 g, 124.84 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min then a solution of cuprous bromide (3.58 g, 24.96 mmol) in aqueous 46% hydrogen bromide (9.98 g, 124.84 mmol) was added and the reaction was allowed to warm to ambient temperature and stirred for 2 h. The resulting mixture was basified with aqueous ammonium and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulphate and concentrated to afford the crude compound. Purification by column chromatography over silica gel (100-200 mesh) with 20% ethyl acetate in petroleum ether as eluent afforded 5-bromoisoquinoline (2.3 g, 53%) as a pale yellow solid.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9]Cl)=[CH:5][C:4]=1[S:11][CH3:12].[C-:13]#[N:14].[K+]>CS(C)=O>[CH3:12][S:11][C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][C:3]=1[S:2][CH3:1])[CH2:9][C:13]#[N:14]
Reactant: CSc1ccc(CCl)cc1SC
Reactant: [C-]#N
Agent: [K+]
Solvent: CS(C)=O
Product: CSc1ccc(CC#N)cc1SC
Temperature: 0 °C

Procedure:
42.5 g (0.194 mol) of 1,2-bis(methylthio)-4-chloromethyl-benzene and 25.3 g (0.388 mol) of potassium cyanide are stirred at ambient temperature in 200 ml of DMSO. When the starting material can no longer be detected by GC analysis, the brown solution is poured into ice/water and extracted with acetic acid acetate and the organic phase is dried over magnesium sulfate. After evaporation 34.8 g (85.7%) of 3,4-bis(methylthio)-benzyl cyanide are obtained as brown substance. The 1H-NMR-spektra data (CDCl3) are in accordance with the proposed structure of the compound: 7.24-7.06 ppm (s and d, 3 aromatic H), 3.70 ppm (s, 2H), 2.47 ppm (s, CH3S) and 2.45 ppm (2 s, CH3S).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:8][C:9](=[S:18])[NH:10][C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1.[H-].[K+].Br[CH:22](Br)[CH3:23].O>CN(C)C=O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:8]2[C:9]([S:18][CH2:22][CH2:23]2)=[N:10][C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1
Reactant: S=c1[nH]c(-c2ccccn2)c(-c2ccccn2)[nH]1
Reactant: CC(Br)Br
Agent: [H-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: c1ccc(-c2nc3n(c2-c2ccccn2)CCS3)nc1
Reaction time: 2 h

Procedure:
A mixture of 16.57 g (0.065 m) of 4,5-di(2-pyridyl)-1H-imidazole-2-thione in 150 ml of dimethylformamide was stirred at -15° (ice-methanol-dry ice) under nitrogen and 27 ml (6.2 g, 0.15 m) of a 24% suspension of potassium hydride in mineral oil was added gradually. After about 2 hours, a solution of 11.8 g (5.42 ml, 0.0634 m) of dibromoethane in 60 ml of dimethylformamide was added dropwise. The reaction mixture was allowed to attain room temperature overnight. The mixture was poured into 600 ml of water. The aqueous mixture was extracted with 3×200 ml portions of methylenechloride. The combined extracts were washed with 5×100 ml water, brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was triturated under 25 ml of low boiling petroleum ether. The product was separated, dissolved in 50 ml of ethanol. The solution was chilled until crystallization was complete, filtered, and the product was washed with a small portion of cold ethanol and air dried. Yield 9.1 g, m.p. 140°-142°. Crystallization three times from ethanol gave an analytical sample of 5,6-di-(2-pyridyl)-2,3-dihydroimidazo[2,1-b]thiazole, m.p. 142°-143°.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:9])=[N:6][C:7]=1[Cl:8].[C:10](N1C=CC=CC1=O)(N1C=CC=CC1=O)=[S:11]>ClCCl.C(OCC)(=O)C.CCCCCC>[Cl:8][C:7]1[C:2]([Cl:1])=[CH:3][CH:4]=[C:5]([N:9]=[C:10]=[S:11])[N:6]=1
Reactant: O=c1ccccn1C(=S)n1ccccc1=O
Reactant: Nc1ccc(Cl)c(Cl)n1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: S=C=Nc1ccc(Cl)c(Cl)n1
Temperature: 40 °C
Reaction time: 3 h
Yield: 81.3 %

Procedure:
To 5,6-dichloropyridin-2-amine (0.47 g, 2.88 mmol) in dichloromethane (25 mL) was added 1,1′-thiocarbonyldipyridin-2(1H)-one (0.68 g, 2.94 mmol). The reaction was stirred at 40° C. for 3 hours, then cooled to room temperature. The crude material was purified by chromatography (Biotage: 25-100% ethyl acetate/hexane) 2,3-dichloro-6-isothiocyanatopyridine (0.48 g, 2.34 mmol, 81% yield) as a white powder. 1H NMR (500 MHz, DMSO-D6) δ ppm 8.26 (d, J=8.55 Hz, 1H), 7.47 (d, J=8.24 Hz, 1H). MS (LC/MS) R.T.=2.83; [M+H]+=204.8.
Reaction SMILES: [Cl:1][CH2:2][C:3]([NH:5][CH2:6][C:7]1[CH:15]=[C:14]2[C:10]([CH2:11][CH2:12][CH2:13]2)=[CH:9][C:8]=1[OH:16])=[O:4].[Cl:17][S:18](O)(=[O:20])=[O:19]>>[Cl:1][CH2:2][C:3]([NH:5][CH2:6][C:7]1[CH:15]=[C:14]2[C:10]([CH2:11][CH2:12][CH2:13]2)=[C:9]([S:18]([Cl:17])(=[O:20])=[O:19])[C:8]=1[OH:16])=[O:4]
Reactant: O=S(=O)(O)Cl
Reactant: O=C(CCl)NCc1cc2c(cc1O)CCC2
Product: O=C(CCl)NCc1cc2c(c(S(=O)(=O)Cl)c1O)CCC2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
70 g (0.29 mole) of 6-(N-chloroacetylaminomethyl)-5-hydroxyindane are dissolved in 150 ml of chlorosulfonic acid, and the mixture is stirred for approx. 30 minutes at room temperature. The mixture is poured into ice water and the product is filtered off with suction. The initially crystalline material becomes oily after a little time and is employed in the next stage in this form without further purification.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:20]([F:23])([F:22])[F:21])=[CH:4][N:3]=1.[CH3:24][O:25][CH2:26][CH2:27][N:28]1[CH2:34][CH2:33][C:32]2[CH:35]=[C:36]([NH2:39])[CH:37]=[CH:38][C:31]=2[CH2:30][CH2:29]1>>[CH3:24][O:25][CH2:26][CH2:27][N:28]1[CH2:34][CH2:33][C:32]2[CH:35]=[C:36]([NH:39][C:2]3[N:7]=[C:6]([NH:8][C:9]4[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:10]=4[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:20]([F:23])([F:22])[F:21])=[CH:4][N:3]=3)[CH:37]=[CH:38][C:31]=2[CH2:30][CH2:29]1
Reactant: COCCN1CCc2ccc(N)cc2CC1
Reactant: CNC(=O)c1cccc(C)c1Nc1nc(Cl)ncc1C(F)(F)F
Product: CNC(=O)c1cccc(C)c1Nc1nc(Nc2ccc3c(c2)CCN(CCOC)CC3)ncc1C(F)(F)F

Procedure:
The title compound was prepared from 2-(2-chloro-5-trifluoromethyl-pyrimidin-4-ylamino)-3,N-dimethyl-benzamide and 3-(2-methoxyethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine in an analogous manner to Example 195 to afford a white solid (29 mg, 47%). Mp: 73-6° C. LCMS (m/e) 529 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.40 (s, 1H), 8.30 (s, 1H), 7.39 (m, 2H), 7.31 (m, 1H), 7.10 (s, 1H), 6.99 (br s, 1H), 6.84 (br s, 1H), 6.00 (br s, 1H), 3.55 (t, 2H, J=5 Hz), 3.39 (s, 3H), 2.88 (d, J=5 Hz, 3H), 2.90 (m, 2H), 2.74 (t, J=5 Hz, 2H), 2.70-2.63 (m, 6H), 2.23 (s, 3H).
Reaction SMILES: [N:1]12[C:7](=[O:8])[CH2:6][CH:5]1[CH2:4][C:3](=[O:9])[CH:2]2[C:10]([O:12]CC1C=CC=CC=1)=[O:11].C(O)C.O.C([O-])(O)=O.[Na+:28]>O1CCOCC1.[Pd]>[N:1]12[C:7](=[O:8])[CH2:6][CH:5]1[CH2:4][C:3](=[O:9])[CH:2]2[C:10]([O-:12])=[O:11].[Na+:28]
Reactant: O=C1CC2CC(=O)N2C1C(=O)OCc1ccccc1
Agent: [Pd]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: C1COCCO1
Product: O=C([O-])C1C(=O)CC2CC(=O)N21

Procedure:
Benzyl 1-azabicyclo[3.2.0]heptan-3,7-dione-2-carboxylate (25 mg) is hydrogenated at 40 psi for 1 hr in dioxane (2 ml) containing ethanol (0.5 ml), H2O (0.5 ml), NaHCO3 (8.1 mg) and 10% Pd/C (10 mg). The mixture is filtered to remove the catalyst which is washed with more H2O (2.5 ml). The combined filtrate and washing is extracted with EtOAc (3×2 ml), concentrated under reduced pressure, and lyophilized to provide sodium 1-azabicyclo[3.2.0]heptan-3,7-dione-2-carboxylate.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[C:8]([Br:10])[CH:7]=[CH:6][C:5]=1[OH:11])(=[O:3])[CH3:2].[O:12]1[CH2:17][CH2:16][CH2:15][C:14](=O)[CH2:13]1.N1CCC[CH2:20]1>CO>[Br:10][C:8]1[CH:9]=[C:4]2[C:5](=[CH:6][C:7]=1[CH3:20])[O:11][C:14]1([CH2:15][CH2:16][CH2:17][O:12][CH2:13]1)[CH2:2][C:1]2=[O:3]
Reactant: CC(=O)c1cc(Br)ccc1O
Reactant: O=C1CCCOC1
Reactant: C1CCNC1
Solvent: CO
Product: Cc1cc2c(cc1Br)C(=O)CC1(CCCOC1)O2
Temperature: 25 °C

Procedure:
A solution of 2-Acetyl-4-bromophenol (920 mg, 4.02 mmol), dihydro-2H-pyran-3(4H)-one (402 mg, 4.02 mmol) and pyrrolidine (0.5 mL) in MeOH (10 mL) was heated to reflux for 2 h. The reaction mixture was cooled down to room temperature and evaporated. The residue was purified by flash chromatography on silica gel eluting with EA in hexane (0-20%) to give 6-bromo-7-methyl-2′,4′,5′,6′-tetrahydrospiro[chroman-2,3′-pyran]-4-one (593 mg); MS ESI+ve m/z 311 (M+H)+.
Reaction SMILES: [Cl:1][C:2]([Cl:10])([Cl:9])[CH2:3][CH2:4][C:5]([CH3:8])(O)[CH3:6].C1(C)C=CC(S(O)(=O)=O)=CC=1>>[Cl:1][C:2]([Cl:10])([Cl:9])[CH2:3][CH2:4][C:5]([CH3:8])=[CH2:6]
Reactant: CC(C)(O)CCC(Cl)(Cl)Cl
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: C=C(C)CCC(Cl)(Cl)Cl
Yield: 9.3 %

Procedure:
Then, to 732 g of 1,1,1-trichloro-4-methyl-4-pentanol was added 7.3 g of p-toluenesulfonic acid and the mixture was heated at 155° - 160° C. for 1.5 hours, the byproduct water being azeotropically removed. The reaction mixture was as such distilled under a reduced pressure of 200 mmHg and the distillate was dried over sodium sulfate and fractionally distilled. By the above procedure was obtained 62 g of 1,1,1-trichloro-4-methyl-4-pentene as a fraction boiling at 73° - 74° C. (20 mmHg), together with 536 g of 1,1,1-trichloro-4-methyl-3-pentene as a fraction boiling at 74° - 77° C. (20 mmHg).
Reaction SMILES: [C@@H:1]1([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18](N)[C:13]=3[CH:12]=[CH:11]2)[O:7][C@H:6]([CH2:8][OH:9])[C@@H:4]([OH:5])[C@@H:2]1[OH:3].C(O)(=[O:22])C.N([O-])=O.[Na+].NC(N)=O>O>[C@@H:1]1([N:10]2[C:14]3[N:15]=[CH:16][NH:17][C:18](=[O:22])[C:13]=3[CH:12]=[CH:11]2)[O:7][C@H:6]([CH2:8][OH:9])[C@@H:4]([OH:5])[C@@H:2]1[OH:3]
Reactant: CC(=O)O
Reactant: Nc1ncnc2c1ccn2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O
Agent: NC(N)=O
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: O=c1[nH]cnc2c1ccn2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O

Procedure:
A solution of one g of 7-β-D-arabinofuranosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine, 4.3 ml of glacial acetic acid, 50 ml water, and 2.67 g of sodium nitrite is heated at 75° C. for one hour, cooled, and treated with 2.1 g of urea. The solution is evaporated in vacuo and the resulting residue is dissolved in water and treated with 15 ml of wet Dowex 50×8 (in hydrogen form). The resin is filtered and washed with water. The filtrate is treated with charcoal, filtered and evaporated in vacuo. The residue is recrystallized from water to provide 0.75 g of pure 7-β-D-arabinofuranosyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1.[CH3:14][N:15]([CH3:23])[CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]1[NH2:22].C(N(CC)CC)C>>[CH3:14][N:15]([CH3:23])[C@@H:16]1[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]1[NH:22][C:7]([C:6]1[CH:10]=[CH:11][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:4][CH:5]=1)=[O:8]
Reactant: CN(C)C1CCCCC1N
Reactant: O=C(Cl)c1ccc(C(F)(F)F)cc1
Solvent: CCN(CC)CC
Product: CN(C)[C@@H]1CCCC[C@H]1NC(=O)c1ccc(C(F)(F)F)cc1

Procedure:
The titled amide was prepared according to general procedure B using p-trifluoromethyl-benzoyl chloride (4.17 g.; 0.02 mole), N,N-dimethylcyclohexane-1,2-diamine (2.84 g.; 0.02 mole) and triethylamine (2.02 g., 0.02 mole). The crude solid was crystallized from ether to give 4.766 g. (77% yield) of colorless needles, m.p. 141°-142°, raised to 141.5°-142.5° on recrystallization. uv λmax 222 nm (ε11,450), sh 245 (5,550); sh 260 (3,400); sh 276 (1.750), ir NH 3310; =CH 3030; N-alkyl 2770, 2740; C=O 1635; C=C 1575, 1510; amide II 1550; CF3 /ether 1330, 1190, 1165, 1130, 1105, 1065, 1020; aromatic 860; nmr in CDCl3 at 100 MHz was in accord. Mass spectrum M+ 314.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][N:13]([CH3:15])[CH3:14].Cl[C:17]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][CH:20]=[CH:19][N:18]=1.C(N(CC)CC)C>O1CCOCC1>[CH3:15][N:13]([CH3:14])[CH2:12][CH2:11][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([NH:1][C:17]3[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][CH:20]=[CH:19][N:18]=3)[CH:3]=2)[NH:7][CH:6]=1
Reactant: CN(C)CCc1c[nH]c2ccc(N)cc12
Reactant: O=[N+]([O-])c1cccnc1Cl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: CN(C)CCc1c[nH]c2ccc(Nc3ncccc3[N+](=O)[O-])cc12
Temperature: 101 °C
Yield: 67 %

Procedure:
5-Amino-3-(2-dimethylaminoethyl)indole and 2-chloro-3-nitropyridine were used. Triethylamine was used as base, p-dioxane was used as solvent, and the reaction was heated at reflux (101° C.) for 3 hours. Chromatography afforded the title compound (67%) as a dark red foam: mp, 59.0°-61.0° C.; 1H NMR (CDCl3) δ 8.66 (br s, 1H), 8.51 (dd, J=8.3 and 1.8 Hz, 1H), 8.41 (dd, J=4.4 and 1.8 Hz, 1H), 7.76 (br s, 1H), 7.30-7.24 (m, 2H), 6.97 (d, J=2.1 Hz, 1H), 6.73 (dd, J=8.3 and 4.4 Hz, 1H), 2.97-2.91 (m, 2H), 2.70-2.63 (m, 2H), 2.36 (s, 6H); 13C NMR (CDCl3) δ 155.7, 151.5, 135.5, 134.5, 129.4, 128.2, 127.9, 122.8, 119.3, 114.4, 114.3, 113.0, 111.5, 60.3, 45.4, 23.7. Anal. calcd for C17H19N5O2.1/3 H2O: C, 61.62; H, 5.98; N, 21.13. Found: C, 61.58; H, 5.65; N, 20.80.
Reaction SMILES: C(O[C:9]([N:11](C)[N:12]1[C:21]([C:22]([OH:24])=[O:23])=[C:20]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([Cl:31])[CH:18]=2)[C:13]1=[O:32])=O)C1C=CC=CC=1.[CH2:34]1[CH2:39][CH2:38][CH:37]([CH2:40]O)[CH2:36][CH2:35]1>>[CH:37]1([CH2:40][O:24][C:22]([C:21]2[N:12]([NH:11][CH3:9])[C:13](=[O:32])[C:14]3[C:19]([C:20]=2[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[CH:18][C:17]([Cl:31])=[CH:16][CH:15]=3)=[O:23])[CH2:38][CH2:39][CH2:34][CH2:35][CH2:36]1
Reactant: OCC1CCCCC1
Reactant: CN(C(=O)OCc1ccccc1)n1c(C(=O)O)c(-c2ccccc2)c2cc(Cl)ccc2c1=O
Product: CNn1c(C(=O)OCC2CCCCC2)c(-c2ccccc2)c2cc(Cl)ccc2c1=O

Procedure:
The present compound was synthesized by a method similar to that in Example 207 and using 2-[(benzyloxycarbonyl)(methyl)amino]-6-chloro-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid (200 mg) and 4-cyclohexylmethylalcohol.
Reaction SMILES: [O-:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na+].Cl[C:10]1[CH:11]=[C:12]2[C:17](=[O:18])[N:16]([CH3:19])[C:14](=[O:15])[C:13]2=[CH:20][CH:21]=1>>[O:1]([C:10]1[CH:11]=[C:12]2[C:17](=[O:18])[N:16]([CH3:19])[C:14](=[O:15])[C:13]2=[CH:20][CH:21]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CN1C(=O)c2ccc(Cl)cc2C1=O
Reactant: [O-]c1ccccc1
Agent: [Na+]
Product: CN1C(=O)c2ccc(Oc3ccccc3)cc2C1=O
Temperature: 250 °C
Yield: 45.6 %

Procedure:
A mixture of 0.440 g (3.80 mmol) of anhydrous sodium phenoxide and 1.50 g (76.7 mmol) of 4-chloro-N-methyl phthalimide is heated to 250° C. for 4 hours under a nitrogen gas atmosphere in an autoclave. There was obtained a 45.6% yield of 4-phenoxy-N-methyl phthalimide based on the phenoxide as determined by gas or liquid chromatographic analysis using o-terphenyl as an internal standard. The product was identified by a comparison of its retention time with that of an authentic sample of the desired material in a conventional matter.
Reaction SMILES: [C:1]1([C:7]2[O:8][C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=3[C:11](=O)[N:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.[NH2:19][NH2:20]>C(O)C>[OH:8][C:9]1[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=1[C:11]1[N:12]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[NH:20][N:19]=1
Reactant: NN
Reactant: O=c1nc(-c2ccccc2)oc2ccccc12
Solvent: O
Solvent: CCO
Product: Oc1ccccc1-c1n[nH]c(-c2ccccc2)n1

Procedure:
1.9 g of 2-phenyl-benzo[e][1,3]oxazin-4-one are refluxed in 75 ml of ethanol with 1.0 g of hydrazine hydrate. After about 1 hour the solvent is distilled off in vacuo and the residue remaining is stirred into water. The solid formed (3-(2-hydroxyphenyl)-5-phenyl-1,2,4-triazole) is used in the next step without further purification. Yield: 0.5 g (25%).
Reaction SMILES: CC1C=C[C:5]([CH2:6][S:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=CC=1.ICC.CC[O-].[Na+].SCC(OCC)=O>C(O)C>[CH2:6]([S:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH3:5]
Reactant: CCOC(=O)CSCc1ccc(C)cc1
Agent: CCOC(=O)CS
Agent: CC[O-]
Agent: [Na+]
Solvent: CCI
Solvent: CCO
Product: CCOC(=O)CSCC

Procedure:
The procedure is as in Example 29 for the preparation of ethyl (4-methylbenzylthio)acetate, starting with iodoethane (10.5 g), a 2M ethanolic solution of sodium ethylate (37 cc) and ethyl 2-mercaptoacetate (8.1 g) in ethanol (100 cc). Ethyl (ethylthio)acetate (6.9 g) is thereby obtained, and is used in the crude state in the subsequent syntheses.