Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([CH:4]([C:6]1[N:7]=[C:8]2[S:16][CH:15]=[C:14]([CH3:17])[N:9]2[C:10](=[O:13])[C:11]=1Br)[CH3:5])=[N+:2]=[N-:3].[F:18][C:19]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.C(OCC)(=O)C.C(P([Pd]P(C1C=CC(N(C)C)=CC=1)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C>[N:1]([CH:4]([C:6]1[N:7]=[C:8]2[S:16][CH:15]=[C:14]([CH3:17])[N:9]2[C:10](=[O:13])[C:11]=1[C:23]1[CH:22]=[CH:21][CH:20]=[C:19]([F:18])[C:24]=1[F:25])[CH3:5])=[N+:2]=[N-:3]
Reactant: OB(O)c1cccc(F)c1F
Reactant: Cc1csc2nc(C(C)N=[N+]=[N-])c(Br)c(=O)n12
Agent: CN(C)c1ccc([PH]([Pd][PH](c2ccc(N(C)C)cc2)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: Cc1csc2nc(C(C)N=[N+]=[N-])c(-c3cccc(F)c3F)c(=O)n12
Temperature: 100 °C
Reaction time: 8 h
Yield: 62.9 %

Procedure:
To a mixture of 7-(1-azidoethyl)-6-bromo-3-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (0.12 g, 0.38 mmol) and (2,3-difluorophenyl)boronic acid (0.072 g, 0.46 mmol) in 1,4-dioxane (3 mL) was added a 1N solution of sodium carbonate in water (0.57 mL, 0.57 mmol) and dichloro(bis{di-tert-butyl[4-(dimethylamino)phenyl]phosphoranyl}palladium (0.014 g, 0.019 mmol). The mixture was stirred at 100° C. overnight. After cooling, the mixture was diluted with ethyl acetate, washed with water, dried over Na2SO4, concentrated, and purified on silica gel (0-30% ethyl acetate/hexane) to give the desired product (83 mg). LCMS calculated for C15H12F2N5OS (M+H)+: m/z=348.1. Found: 348.0.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][CH2:14][CH3:15])=[CH:8][CH:7]=1.[N:16]1[CH:21]=[C:20]([CH3:22])[CH:19]=[C:18]([CH3:23])[CH:17]=1>C(#N)C>[Br-:1].[CH2:12]([C:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][CH2:3][CH2:2][N+:16]2[CH:21]=[C:20]([CH3:22])[CH:19]=[C:18]([CH3:23])[CH:17]=2)=[CH:7][CH:8]=1)[CH2:13][CH2:14][CH3:15]
Reactant: Cc1cncc(C)c1
Reactant: CCCCc1ccc(CCCCBr)cc1
Solvent: CC#N
Product: CCCCc1ccc(CCCC[n+]2cc(C)cc(C)c2)cc1
Product: [Br-]
Yield: 81 %

Procedure:
1-(4-Bromo-butyl)-4-butyl-benzene (1 mmol) was added to a solution of 3,5-lutidine (3 mmol) in acetonitrile, and the solution was refluxed for 24 hours. The acetonitrile was removed in a vacuum, and the resulting residue was partitioned between ether and water. The aqueous layer was washed extensively with ether until no lutidine was left in the aqueous layer. The resulting aqueous solution of the product was extracted with chloroform. The chloroform was removed to afford the product (81%). 1HNMR (300 MHz, CDCl3, ppm), 9.11 (s, 2H), 7.92 (s, 1H), 7.00-7.06 (m, 4H), 4.88 (t, J=7.5, 2H), 2.51-2.62 (m, 7H), 1.99-2.05 (m, 2H), 1.49-1.66 (m, 4H), 1.28-1.35 (m, 2H), 0.89 (t, J=7.2, 3H). 13CNMR, 146.17, 141.96, 140.81, 138.91, 138.40, 128.63, 128.48, 61.60, 35.54, 34.98, 34.05, 31.68, 27.95, 22.72, 18.88, 14.31.
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[F:13][C:14]([F:22])([F:21])[CH:15]([OH:20])[C:16]([F:19])([F:18])[F:17].C(N(CC)C(C)C)(C)C.[CH3:32][C:33]1[CH:34]=[C:35]([C:39]2[CH:44]=[CH:43][C:42]([CH2:45][N:46]3[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]3)=[C:41]([O:52][C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[CH:40]=2)[CH:36]=[CH:37][CH:38]=1>O.ClCCl>[CH3:32][C:33]1[CH:34]=[C:35]([C:39]2[CH:44]=[CH:43][C:42]([CH2:45][N:46]3[CH2:47][CH2:48][N:49]([C:2]([O:20][CH:15]([C:16]([F:19])([F:18])[F:17])[C:14]([F:22])([F:21])[F:13])=[O:4])[CH2:50][CH2:51]3)=[C:41]([O:52][C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[CH:40]=2)[CH:36]=[CH:37][CH:38]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: OC(C(F)(F)F)C(F)(F)F
Reactant: Cc1cccc(-c2ccc(CN3CCNCC3)c(Oc3ccccc3)c2)c1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1cccc(-c2ccc(CN3CCN(C(=O)OC(C(F)(F)F)C(F)(F)F)CC3)c(Oc3ccccc3)c2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 184.2 %

Procedure:
A 100 mL round-bottom flask, was charged with triphosgene (50.0 mg, 0.170 mmol, 0.30 equiv), dichloromethane (10 mL), 1,1,1,3,3,3-hexafluoropropan-2-ol (94.0 mg, 0.560 mmol, 1.00 equiv). N,N-Diisopropylethylamine (144 mg, 1.00 mmol, 2.00 equiv) was added dropwise. The resulting solution was stirred for 2 h at room temperature. 1-[[4-(3-Methylphenyl)-2-phenoxyphenyl]methyl]piperazine (200 mg, 0.560 mmol, 1.00 equiv) was added. The resulting solution was stirred overnight at room temperature and then diluted with water (5 mL). The resulting mixture was extracted with dichloromethane (2×10 mL) and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product (230 mg) was purified by preparative HPLC using the following gradient conditions: 20% CH3CN/80% Phase A increasing to 80% CH3CN over 10 min, then to 100% CH3CN over 0.1 min, holding at 100% CH3CN for 1.9 min, then reducing to 20% CH3CN over 0.1 min, and holding at 20% for 1.9 min, on a Waters 2767-5 Chromatograph. Column: Xbridge Prep C18, 19*150 mm 5 um; Mobile phase: Phase A: aqueous NH4HCO3 (0.05%); Phase B: CH3CN; Detector, UV220 & 254 nm. Purification resulted in 173 mg (56% yield) of 1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[4-(3-methylphenyl)-2-phenoxyphenyl]methyl]piperazine-1-carboxylate as yellow oil. 1H NMR 300 MHz (CDCl3) δ 7.51 (d, J=7.8 Hz, 1H), 7.27-7.39 (m, 5H), 7.21-7.248 (m, 1H), 7.18 (d, J=1.5 Hz, 1H), 7.12-7.14 (m, 1H), 7.02-7.07 (m, 1H), 6.92-6.96 (m, 2H), 5.71-5.79 (m, 1H), 3.62 (s, 2H), 3.50 (br, 4H), 2.50-2.51 (m, 4H), 2.37 (s, 3H). LCMS (ESI, m/z): 553 [M+H]+.
Reaction SMILES: O.OC1C2N=NNC=2C=CC=1.Cl.[CH3:13][O:14][CH2:15][CH2:16][N:17]([CH2:24][C:25]1[CH:26]=[C:27]([CH:43]=[CH:44][CH:45]=1)[CH2:28][CH2:29][NH:30][C:31]1[C:32](=[O:42])[N:33]([CH2:38][C:39](O)=[O:40])[C:34]([CH3:37])=[CH:35][N:36]=1)[C:18](=[O:23])[C:19]([F:22])([F:21])[F:20].CN1CCOCC1.[CH3:53][C:54]1[C:62]2[C:57](=[CH:58][CH:59]=[C:60]([CH2:63][NH2:64])[CH:61]=2)[NH:56][CH:55]=1>CN(C)C=O>[F:21][C:19]([F:20])([F:22])[C:18]([N:17]([CH2:16][CH2:15][O:14][CH3:13])[CH2:24][C:25]1[CH:45]=[CH:44][CH:43]=[C:27]([CH2:28][CH2:29][NH:30][C:31]2[C:32](=[O:42])[N:33]([CH2:38][C:39]([NH:64][CH2:63][C:60]3[CH:61]=[C:62]4[C:57](=[CH:58][CH:59]=3)[NH:56][CH:55]=[C:54]4[CH3:53])=[O:40])[C:34]([CH3:37])=[CH:35][N:36]=2)[CH:26]=1)=[O:23]
Reactant: Cc1c[nH]c2ccc(CN)cc12
Reactant: COCCN(Cc1cccc(CCNc2ncc(C)n(CC(=O)O)c2=O)c1)C(=O)C(F)(F)F
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: CN(C)C=O
Solvent: O
Solvent: CN1CCOCC1
Product: COCCN(Cc1cccc(CCNc2ncc(C)n(CC(=O)NCc3ccc4[nH]cc(C)c4c3)c2=O)c1)C(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Hydroxybenzotriazole hydrate (60 mg, 0.44 mmol) and WSCDl.HCl (93 mg, 0.47 mmol) were added to a solution of 2-[3-[(3-{[(2-methoxyethyl)(2,2,2-trifluoroacetyl)amino]methyl}phenethyl)amino]-6-methyl-2-oxo-1(2H)-pyrazinyl]acetic acid (190 mg, 0.40 mmol) [see preparation 44] in N,N-dimethylformamide (3.0 ml). N-methylmorpholine (123 mg, 1.2 mmol) was added followed by (3-methyl-1H-indol-5-yl)methylamine (72 mg, 0.45 mmol) [see preparation 36]. The reaction mixture was stirred at room temperature for 18 hrs, after which time the mixture was partitioned between ethyl acetate (30 ml) and water (30 ml). The organic layer was washed with water (3×30 ml), brine (30 ml) and dried over MgSO4 and the solvent evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using an elution gradient of dichloromethane:methanol:0.88 ammonia (99:1:0.1) changing to (98:2:0.2) to afford the title compound as a oil, 113 mg (53%).
Reaction SMILES: [Mg].Br[CH2:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH2:12]([SiH:15](Cl)Cl)[CH:13]=[CH2:14].[Na+].[Cl-]>C(OCC)C>[CH2:12]([SiH:15]([CH2:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH:13]=[CH2:14]
Reactant: C=CC[SiH](Cl)Cl
Reactant: BrCCCc1ccccc1
Agent: [Cl-]
Agent: [Mg]
Agent: [Na+]
Solvent: CCOCC
Product: C=CC[SiH](CCCc1ccccc1)CCCc1ccccc1
Temperature: 25 °C
Reaction time: 10 h
Yield: 86 %

Procedure:
To a 500 mL Schlenk flask containing magnesium turnings (2.71 g, 111.5 mmol) in diethyl ether (250 mL) was added dropwise a solution of 1-bromo-3-phenylpropane (20.0 g, 100.5 mmol) over 4 hours. The resulting pale yellow solution was stirred for 10 hours at room temperature then cooled to 0° C. and treated with allyldichlorosilane (7.085 g, 50 mmol) via syringe. The resulting white slurry was stirred for 4 hours at room temperature then heated to reflux for 20 minutes. After filtration and aqueous work-up, the solvent was removed in vacuo to give a colorless liquid. Yield: 86%. FTIR (NaCl, cm−1): 3083, 3066, 3021, 2927, 2842, 2069, 1598, 1569, 1488, 1456, 1142, 1067, 1025, 987, 920, 891, 834, 745, 701. 1H NMR (CDCl3): 7.28, 7.17, 5.74, 4.89, 4.54, 3.74, 2.62, 1.67, 0.64.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH:17]=O)[CH:12]=2)[CH:3]=1.CN.[C:21]([BH3-])#[N:22].[Na+].[C:25]([OH:32])(=[O:31])/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29]>C(O)(=O)C.CO>[C:25]([OH:32])(=[O:31])/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29].[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][NH:22][CH3:21])[CH:12]=2)[CH:3]=1
Reactant: [BH3-]C#N
Reactant: N#Cc1ccc(Cl)cc1Oc1cccc(C=O)c1
Agent: CN
Agent: O=C(O)/C=C/C(=O)O
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CNCc1cccc(Oc2cc(Cl)ccc2C#N)c1
Yield: 58.4 %

Procedure:
4-Chloro-2-(3-formyl-phenoxy)-benzonitrile (0.52 g, 2.02 mmol), methylamine (2M in methanol, 1.0 ml, 2.0 mmol) and sodium cyanoborohydride (0.14 g, 2.2 mmol) Were stirred at ambient temperature in a 1% acetic acid/methanol solution (30 ml) for 18 h. The solvent was removed in vacuo. The residue was treated with 10% aqueous sodium carbonate and extracted with ethyl acetate. The ethyl acetate layer was separated and washed with water, brine and dried over MgSO4. After filtration, fumaric acid (0.23 g, 2.0 mmol) was added to the filtrate and the solvent removed in vacuo. The residue was triturated with ethyl acetate overnight, filtered and dried to give 4-chloro-2-(3-methylaminomethyl-phenoxy)-benzonitrile fumarate (454 mg, 58%) as a white solid.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:24]=[C:11]3[N:12]=[C:13]([NH:22][NH2:23])[CH:14]=[C:15]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[N:10]3[N:9]=2)=[CH:4][CH:3]=1.C(O)(=O)C.[C:29]1([CH3:37])[CH:34]=[CH:33][CH:32]=[C:31]([CH:35]=O)[CH:30]=1>C(O)C>[CH3:37][C:29]1[CH:30]=[C:31]([CH:32]=[CH:33][CH:34]=1)[CH:35]=[N:23][NH:22][C:13]1[CH:14]=[C:15]([N:16]2[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)[N:10]2[N:9]=[C:8]([C:5]3[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=3)[CH:24]=[C:11]2[N:12]=1
Reactant: Cc1cccc(C=O)c1
Reactant: Cc1ccc(-c2cc3nc(NN)cc(N4CCOCC4)n3n2)cn1
Solvent: CC(=O)O
Solvent: CCO
Product: Cc1cccc(C=NNc2cc(N3CCOCC3)n3nc(-c4ccc(C)nc4)cc3n2)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 53 %

Procedure:
There was suspended, in ethanol (3 mL), [2-(6-methyl-pyridin-3-yl)-7-morpholin-4-yl-pyrazolo[1,5-a]pyrimidin-5-yl]-hydrazine (70 mg, 0.22 mM) prepared in the preceding step 2, then acetic acid (6.3 μL, 0.11 mM) and metatolualdehyde (28 μL, 0.24 mM) were added to the suspension and the mixture was stirred at room temperature for 16 hours. The precipitated solid was recovered through filtration and then washed with diethyl ether to thus give the title compound (50.2 mg, yield: 53%).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH2:3][CH:2]1[CH2:10]O.[C:12]1(=[O:22])[NH:16][C:15](=[O:17])[C:14]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:13]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH2:3][CH:2]1[CH2:10][N:16]1[C:12](=[O:22])[C:13]2[C:14](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:15]1=[O:17]
Reactant: OCC1Cc2ccccc2O1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1CC1Cc2ccccc2O1
Temperature: 25 °C
Reaction time: 20 h
Yield: 116.5 %

Procedure:
To a mixture of (2,3-dihydro-benzofuran-2-yl)-methanol (1.65 g, 11 mmol), phthalimide (3.24 g, 22 mmol), and triphenylphosphine (5.77 g, 22 mmol) in THF (40 mL) is added diethyl azodicarboxylate (3.46 mL, 22 mmol) at −10° C., and the mixture is allowed to warm to room temperature. After 20 h at rt, the mixture is concentrated in vacuo, and the residue is chromatographed on SiO2 (40% EtOAc in heptane) to afford 2-(2,3-dihydro-benzofuran-2-ylmethyl)-isoindole-1,3-dione (3.58 g). LCMS: RT=2.64 minutes; MS: 280 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]([CH2:8][CH2:9][CH2:10][C:11]#[CH:12])=NC=1.CCCCCCC.C(OCC)(=O)C>[N+](C1C=CC=CC=1)([O-])=O>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=1
Reactant: C#CCCCc1ncc(Cl)cn1
Solvent: CCOC(C)=O
Solvent: CCCCCCC
Solvent: O=[N+]([O-])c1ccccc1
Product: Clc1cnc2c(c1)CCC2

Procedure:
A solution of 5-chloro-2-(pent-4-ynyl)pyrimidine (H. C. van der Plas, Tetrahedron 1989, 45, 5151-5162) (4.95 g (27.4 mmol) in nitrobenzene (50 ml) was heated to 210° C. for 1.5 hours under a continuous stream of nitrogen. The reaction was followed by TLC (silica gel, heptane:ethyl acetate=2:1; UV detection 254 nm). After completion, the reaction mixture was purified by flash chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 80:20 as the eluent. The 3-chloro-6,7-dihydro-5H-[1]pyrindine was obtained as a light brown solid (3.21 g, 76% yield). MS (ISP): m/z=154 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[C:7]2[CH:8]=[C:9]([C:12]3[NH:16][C:15]([C:17]#[N:18])=[CH:14][CH:13]=3)[CH:10]=[CH:11][C:6]=2[NH:5][C:4](=[O:19])[O:3]1.[C:21]([O:25][C:26](=[O:29])[CH2:27]Br)([CH3:24])([CH3:23])[CH3:22]>>[C:21]([O:25][C:26](=[O:29])[CH2:27][N:16]1[C:12]([C:9]2[CH:10]=[CH:11][C:6]3[NH:5][C:4](=[O:19])[O:3][C:2]([CH3:20])([CH3:1])[C:7]=3[CH:8]=2)=[CH:13][CH:14]=[C:15]1[C:17]#[N:18])([CH3:24])([CH3:23])[CH3:22]
Reactant: CC1(C)OC(=O)Nc2ccc(-c3ccc(C#N)[nH]3)cc21
Reactant: CC(C)(C)OC(=O)CBr
Product: CC(C)(C)OC(=O)Cn1c(C#N)ccc1-c1ccc2c(c1)C(C)(C)OC(=O)N2

Procedure:
5-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrol-2-carbonitrile (5.4 g, 20 mmol) and tert-butylbromoacetate (4.64 g, 22 mmol) were reacted, according to General Method A, to afford the title compound, m.p. 188-190° C. (3 g, 40%). 1H-NMR (DMSO-d6) δ1.35 (s, 9H), 1.62 (s, 6H), 4.8 (s, 2H), 6.35 (d, J=4.3 Hz, 1H), 6.98 (d, J=8.1 Hz, 1H), 7.09 (d, J=4.3 Hz, 1H), 7.26 (m, 2H), 10.42 (s, 1H), MS (APCI (−)) m/z 380 (M−H)−
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][CH2:10][O:11][C:12](=[O:14])[CH3:13])=[CH:4][CH:3]=1.[CH2:16]([SH:19])[CH2:17][SH:18].[OH-].[Na+]>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:9][CH2:10][O:11][C:12](=[O:14])[CH3:13])[S:19][CH2:16][CH2:17][S:18]2)=[CH:4][CH:3]=1
Reactant: SCCS
Reactant: CC(=O)OCCC(=O)c1ccc(F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CC(=O)OCCC1(c2ccc(F)cc2)SCCS1
Temperature: 25 °C
Reaction time: 16 h
Yield: 66.1 %

Procedure:
To a solution of acetic acid [3-(4-fluorophenyl)-3-oxo-propyl]ester (2.0 g, 9.52 mmol) in dry dichloromethane (40 ml) are added 1,2-ethanedithiol (1.79 g, 19.0 mmol) and boron trifluoride diethyl ether complex (0.68 g, 4.76 mmol) at 0° C. The resulting reaction mixture is stirred at RT for 16 h. After completion of reaction, the mixture is neutralized with 10M aqueous sodium hydroxide and extracted with DCM (3×100 ml). The combined organic layers are washed with water (100 ml), brine (100 ml), dried over anhydrous sodium sulfate and evaporated in vacuo to get the crude, which is purified by column chromatography (silica gel, 5% ethyl acetate/hexane) to yield acetic acid 2-[2-(4-fluorophenyl)-[1,3]dithiolan-2-yl]-ethyl ester (1.80 g, 6.29 mmol, 66%).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-])=O)=[CH:7][C:6]=1[C:14]([F:17])([F:16])[F:15])(=[O:4])=[O:3].[Cl-].[NH4+].O>C(O)C.[Fe]>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][C:6]=1[C:14]([F:15])([F:16])[F:17])(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccc([N+](=O)[O-])cc1C(F)(F)F
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CS(=O)(=O)c1ccc(N)cc1C(F)(F)F
Yield: 76.2 %

Procedure:
A mixture of 4-(methylsulfonyl)-3-(trifluoromethyl)nitrobenzene (1.55 g, 5.76 mmol), iron powder (1.61 g, 28.8 mmol), and ammonium chloride (0.03.1 g, 0.58 mmol) in ethanol (30 mL), and water (8 mL) was heated at reflux temperature for 1 hour. After cooling, insolubles were filtered off by Celite, and volatiles were removed by evaporation. The residue was redissolved in ethyl acetate (50 mL) and the whole washed with water and brine. After dried over MgSO4 and concentration in vacuo. The residue was washed with hexane to give the subtitle compound (1.05 g, 76.2%, yield).
Reaction SMILES: [C:1]1([C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([CH2:11][CH2:12][CH2:13][NH:14][CH3:15])[C:8]([NH2:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:23][CH2:24][C:25]1[CH:34]=[CH:33][C:28]2[O:29][CH2:30][CH2:31][O:32][C:27]=2[CH:26]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]1([C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([CH2:11][CH2:12][CH2:13][N:14]([CH2:23][CH2:24][C:25]2[CH:34]=[CH:33][C:28]3[O:29][CH2:30][CH2:31][O:32][C:27]=3[CH:26]=2)[CH3:15])[C:8]([NH2:10])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: BrCCc1ccc2c(c1)OCCO2
Reactant: CNCCCC(C(N)=O)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CN(CCCC(C(N)=O)(c1ccccc1)c1ccccc1)CCc1ccc2c(c1)OCCO2

Procedure:
A mixture containing 2,2-diphenyl-5-methylaminopentanamide (0.36 g-see Preparation 1), 6-(2-bromoethyl)-1,4-benzodioxan (0.32 g), anhydrous potassium carbonate (0.75 g) and acetonitrile (20 ml) was heated under reflux for 16 hours. The mixture was partitioned between dichloromethane (50 ml) and 10% aqueous sodium carbonate (30 ml), the layers separated and the aqueous layer extracted with dichloromethane (3×20 ml). The combined dichloromethane extracts were dried (MgSO4) and concentrated in vacuo to give an oil which was purified by column chromatography on silica eluting with dichloromethane containing methanol (0% up to 5%). The product-containing fractions were combined and concentrated in vacuo to give a foam which was further purified by column chromatography on alumina eluting with dichloromethane containing methanol (0% up to 5%). The product-containing fractions were combined and concentrated in vacuo to give the title compound as a foam, yield 0.11 g.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[CH:23]([F:25])[F:24])[N:3]=1.[CH2:26]([NH2:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>O1CCOCC1.O>[CH2:26]([NH:33][C:2]1[N:3]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[CH:23]([F:24])[F:25])[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:7]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: NCc1ccccc1
Reactant: FC(F)c1nc2ccccc2n1-c1nc(Cl)nc(N2CCOCC2)n1
Solvent: O
Solvent: C1COCCO1
Product: FC(F)c1nc2ccccc2n1-c1nc(NCc2ccccc2)nc(N2CCOCC2)n1
Yield: 66.8 %

Procedure:
A mixture of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole (92 mg, 0.25 mmol) and benzylamine (67 mg, 0.625 mmol) in dioxane (5 mL) was heated to reflux for 5 min and cooled. The mixture was diluted with water to give a white precipitate, which was recrystallised from EtOH to give 73 mg (67% yield) of N-benzyl-4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-amine: mp 185-188° C.; 1H NMR (CDCl3) (rotamers) δ 8.41 and 8.28 (2d, J=7.4 and 7.7 Hz, 1H), 7.89 (m, 1H), 7.64 and 7.50 (2t, JHF=53.8 and 53.7 Hz, 1H), 7.43-7.29 (m, 7H), 5.62 (m, exchangeable with D2O, 1H), 4.72 and 4.68 (2d, J=6.0 and 5.9 Hz, 2H), 3.89 (m, 4H), 3.78 (m, 4H); Anal. Calc. for C22H21F2N7O: C, 60.4; H, 4.8; N, 22.4. Found: C, 60.6; H, 4.8; N, 22.7%.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:24]4[O:23][CH2:22][C@H:21]([CH3:25])[N:20](C(OC(C)(C)C)=O)[CH2:19][C:18]=4[C:17]([F:33])=[C:16]([Cl:34])[CH:15]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.C(Cl)Cl.C(N(CC)C(C)C)(C)C.[CH3:47][S:48](Cl)(=[O:50])=[O:49]>>[Cl:34][C:16]1[CH:15]=[C:14]([CH:12]([N:8]2[C:4]3=[N:5][CH:6]=[N:7][C:2]([NH2:1])=[C:3]3[C:10]([CH3:11])=[N:9]2)[CH3:13])[C:24]2[O:23][CH2:22][C@H:21]([CH3:25])[N:20]([S:48]([CH3:47])(=[O:50])=[O:49])[CH2:19][C:18]=2[C:17]=1[F:33]
Reactant: Cc1nn(C(C)c2cc(Cl)c(F)c3c2OC[C@H](C)N(C(=O)OC(C)(C)C)C3)c2ncnc(N)c12
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nn(C(C)c2cc(Cl)c(F)c3c2OC[C@H](C)N(S(C)(=O)=O)C3)c2ncnc(N)c12
Temperature: 0 °C
Reaction time: 1 h

Procedure:
tert-Butyl (3S)-9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-fluoro-3-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (13 mg, 0.026 mmol) was stirred in methylene chloride (100 μL, 2 mmol) with N,N-diisopropylethylamine (14 μL, 0.079 mmol) and cooled to 0° C. Methanesulfonyl chloride (2.6 μL, 0.034 mmol) was added, and the mixture was stirred at 0° C. for 1 hr. The mixture was evaporated and diluted with methanol. The reactions were purified by prep HPLC on C-18 column eluting water:acetonitrile gradient buffered pH 10 to give two enantiomers: Peak #1 (Example 35): LCMS calculated for C19H23ClFN6O3S (M+H)+: m/z=469.1; found: 469.1; Peak #2 (Example 36): LCMS calculated for C19H23ClFN6O3S (M+H)+: m/z=469.1; found: 469.1.
Reaction SMILES: [C:1]([C:4]1[C:5](=[O:19])[NH:6][C:7](=[O:18])[N:8]([CH:17]=1)[C@@H:9]1[O:16][C@H:13]([CH2:14]O)[C@@H:11]([OH:12])[CH2:10]1)(=[O:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N-:39]=[N+:40]=[N-:41].[Na+].C(Br)(Br)(Br)Br>CN(C)C=O>[C:1]([C:4]1[C:5](=[O:19])[NH:6][C:7](=[O:18])[N:8]([CH:17]=1)[C@@H:9]1[O:16][C@H:13]([CH2:14][N:39]=[N+:40]=[N-:41])[C@@H:11]([OH:12])[CH2:10]1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Reactant: [N-]=[N+]=[N-]
Agent: BrC(Br)(Br)Br
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: CC(=O)c1cn([C@H]2C[C@H](O)[C@@H](CN=[N+]=[N-])O2)c(=O)[nH]c1=O
Yield: 58.1 %

Procedure:
1.26 g of 5-acetyl-2'-deoxyuridine, 1.35 g of triphenylphosphine, 1.52 g of sodium azide and 1.7 g of carbon tetrabromide in 40 ml of dimethylformamide were reacted as described in Example 54 and the product was purified by chromatography on 400 g of silica gel in dichloromethane/methanol (9:1) to give 0.80 g of 5-acetyl-5'-azido-2',5'-dideoxyuridine of melting point 159°-162° C. (decomposition).
Reaction SMILES: Cl[CH:2]([C:5](=[O:9])[CH2:6][CH2:7][CH3:8])[CH2:3][CH3:4].[CH3:10][OH:11].C[O-].[Na+]>>[CH3:10][O:11][CH:2]([C:5](=[O:9])[CH2:6][CH2:7][CH3:8])[CH2:3][CH3:4]
Reactant: CO
Reactant: CCCC(=O)C(Cl)CC
Agent: C[O-]
Agent: [Na+]
Product: CCCC(=O)C(CC)OC
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 1.5 grams of 3-chloro-4-heptanone in 3 ml anhydrous methanol (0.01 moles 3-chloro-4-heptanone) is placed into a 25 ml, three-necked, round bottom flask equipped with magnetic stirrer, pot thermometer, reflux condenser (with drying tube), 10 ml addition funnel with nitrogen inlet at top, an ice water-salt bath, and nitrogen bubbler. The 3-chloro-4-heptanone solution is cooled to a temperature of between 0° and 1° C. Into the 10 ml addition funnel is placed a solution of 0.54 grams of sodium methoxide dissolved in 7 ml anhydrous methanol (0.01 moles sodium methoxide). Over a period of one hour, while maintaining the reaction mass at a temperature of between 0° and 1° C., the sodium methoxide solution is added to the 3-chloro-4-heptanone. The reaction mass is then permitted to warm up to room temperature. It is then vacuum filtered thereby separating the white precipitate from the filtrate. The white solid precipitate is washed with 25 ml methylene chloride, and the washings are combined with the filtrate prior to concentration. After concentration of the filtrate, the concentrate is dried over anhydrous sodium sulfate and further concentrated to a weight of 1.0 grams (white oil). The major peak is isolated by GLC trapping (8 feet × 1/4 inch SE-30 column). NMR, IR and mass spectral analyses confirm that the resulting material has the structure ##STR94##