Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:5]=[C:6]=[O:7])[CH2:2][CH2:3][CH3:4].[OH:8][N:9]1[C:14]([CH3:16])([CH3:15])[CH2:13][CH:12]([O:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:11][C:10]1([CH3:27])[CH3:26]>C1(C)C=CC=CC=1>[C:18]([O:17][CH:12]1[CH2:13][C:14]([CH3:16])([CH3:15])[N:9]([O:8][C:6](=[O:7])[NH:5][CH2:1][CH2:2][CH2:3][CH3:4])[C:10]([CH3:27])([CH3:26])[CH2:11]1)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: CCCCN=C=O
Reactant: CC1(C)CC(OC(=O)c2ccccc2)CC(C)(C)N1O
Solvent: Cc1ccccc1
Product: CCCCNC(=O)ON1C(C)(C)CC(OC(=O)c2ccccc2)CC1(C)C
Temperature: 50 °C
Yield: 29.2 %

Procedure:
A solution of 4.66 g (40 mmol) of n-butyl isocyanate in 10 ml of toluene is added over 10 minutes to a suspension of 10.6 g (38.2 mmol) of 1-hydroxy-4-benzoyloxy-2,2,6,6-tetramethylpiperidine in 40 ml of toluene. The reaction mixture is heated at 50° C. for 30 minutes. The reaction mixture is then filtered, and the residue from evaporation of the filtrate is crystallized from hexane to give 4.2 g (29% yield) of a white solid, m.p. 126-27° C.
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][NH:13][C:14]1[S:15][C:16]([C:20](=[O:28])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])=[C:17]([CH3:19])[N:18]=1)(C)(C)C.[ClH:30]>O1CCOCC1>[ClH:30].[NH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][NH:13][C:14]1[S:15][C:16]([C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])=[O:28])=[C:17]([CH3:19])[N:18]=1
Reactant: Cc1ccccc1C(=O)c1sc(NCCCCCNC(=O)OC(C)(C)C)nc1C
Agent: Cl
Solvent: C1COCCO1
Product: Cc1ccccc1C(=O)c1sc(NCCCCCN)nc1C
Yield: 99 %

Procedure:
A solution of 170 mg (0.4 mmol) {5-[4-Methyl-5-(2-methyl-benzoyl)-thiazol-2-ylamino]-pentyl}-carbamic acid tert-butyl ester in 2 ml dioxane was treated with 1 ml 4N HCl in dioxane and allowed to react for 5 h at room temperature. The mixture was evaporated under reduced pressure to afford 143 mg (99%) of the title compound.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8][CH2:7]2)([OH:3])=O.C1(N=C=NC2CCCCC2)CCCCC1.[OH:30][N:31]=[C:32]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.CCOCC>O1CCOCC1.C(Cl)(Cl)Cl>[OH:30][N:31]=[C:32]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:33][CH2:34][N:35]1[CH2:36][CH2:37][N:38]([C:1]([C:4]2[CH:5]=[C:6]3[C:11](=[CH:12][CH:13]=2)[NH:10][C:9](=[O:14])[CH2:8][CH2:7]3)=[O:3])[CH2:39][CH2:40]1
Reactant: O=C1CCc2cc(C(=O)O)ccc2N1
Reactant: ON=C(CCN1CCNCC1)c1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClC(Cl)Cl
Solvent: C1COCCO1
Solvent: CCOCC
Product: O=C1CCc2cc(C(=O)N3CCN(CCC(=NO)c4ccccc4)CC3)ccc2N1
Reaction time: 5 h
Yield: 15.1 %

Procedure:
One gram of 6-carboxy-3,4-dihydrocarbostyril, 1.3 g of dicyclohexylcarbodiimide and 1.47 g of (3-hydroxyimino-3-phenylpropyl)piperazine were suspended in 10 ml of dioxane, then the suspension was stirred at 60° to 70° C. for 5 hours. After the reaction was completed, the solvent was removed by evaporation, to the residue thus obtained was added ether so as to form crystals, then the crystals were removed by filtration. The mother liquor was concentrated, then the residue thus obtained was dissolved by adding chloroform, and the solution was washed with water and an aqueous solution saturated with sodium chloride, then dried with anhydrous potassium carbonate, and the solvent was removed by evaporation. The residue thus obtained was recrystallized from ethanol to yield 320 mg of 6-[4-(3-hydroxyimino-3-phenylpropyl)-1-piperazinylcarbonyl]3,4-dihydrocarbostyril.semihydrate. White powdery substance.
Reaction SMILES: [C:1]1([S:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[C:16](=[O:20])[CH2:15][CH2:14][CH2:13]3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Na].CO>O>[C:1]1([S:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]([OH:20])[CH2:15][CH2:14][CH2:13]3)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1CCCc2cc(S(=O)(=O)c3ccccc3)ccc21
Agent: [Na]
Solvent: CO
Solvent: O
Product: O=S(=O)(c1ccccc1)c1ccc2c(c1)CCCC2O
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.4 %

Procedure:
6-Benzenesulfonyl-3,4-dihydro-2H-naphthalen-I-one (1.31 g, 4.6 mmol) and sodium borohidride (0.35 g, 9.3 mmol) were added to 50 mL methanol, and the reaction mixture was stirred at room temperature for one hour. Water (200 mL was then added to the reaction mixture, resulting in precipitation of white crystals, which were collected by filtration and dried under N2 to give 1.2 g (4.16 mmol, 90%) of 6-benzenesulfonyl-1,2,3,4-tetrahydro-naphthalen-1ol, MS: 289 (M+H)+.
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[CH:7][C:6]=2[CH:5]=[C:4]([C:16]#[N:17])[CH:3]=1.B(O)(O)[C:19]1[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=1>>[O:15]=[C:14]1[C:8]2=[CH:7][C:6]3[CH:5]=[C:4]([C:16]#[N:17])[CH:3]=[C:2]([C:19]4[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=4)[C:10]=3[N:9]2[CH2:11][CH2:12][NH:13]1
Reactant: Cc1ccc(B(O)O)cc1
Reactant: N#Cc1cc(Br)c2c(c1)cc1n2CCNC1=O
Product: Cc1ccc(-c2cc(C#N)cc3cc4n(c23)CCNC4=O)cc1

Procedure:
The title compound, white solid (61 mg, 81%), MS (ISP) m/z=302.5 [(M+H)+], mp 285.5° C., was prepared in accordance with the general method of example 1 from 6-bromo-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-8-carbonitrile (intermediate 15) (72.5 mg, 0.25 mmol) and commercially available p-tolylboronic acid (44.2 mg, 0.325 mmol).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9](=[O:28])[C:10]1[CH:15]=[C:14]([CH3:16])[C:13](Br)=[C:12]([S:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=2[OH:27])[CH:11]=1>CN(C=O)C>[CH3:7][O:8][C:9]([C:10]1[CH:15]=[C:14]([CH3:16])[C:13]2[O:27][C:21]3=[C:22]([Cl:26])[CH:23]=[CH:24][CH2:25][C:20]3=[CH:19][S:18][C:12]=2[CH:11]=1)=[O:28]
Reactant: COC(=O)c1cc(C)c(Br)c(SCc2cccc(Cl)c2O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1cc(C)c2c(c1)SC=C1CC=CC(Cl)=C1O2
Temperature: 80 °C
Reaction time: 4.5 h

Procedure:
Anhydrous potassium carbonate (6.71 g, 48 mmol) was added to a solution of Example 154a (3.9 g, 9.7 mmol) in DMF (200 ml) and the reaction mixture was stirred at 80° C. for 4.5 h. It was concentrated and treated with ethyl acetate, then washed with 10% aqueous HCl, water, brine, dried, concentrated and purified using flash chromatography (silica gel, ethyl acetate/pet ether) to obtain the title compound as a white solid. Yield: 1.2 g (40%); 1H NMR (CDCl3): δ 2.64 (s, 3H, CH3), 3.88 (s, 3H, OCH3), 4.2 (s, 2H, CH2), 7.08 (m, 2H, Ar), 7.32 (q, 1H, Ar), 7.6 (s, 1H, Ar), 7.65 (s, 1H, Ar); MS: m/e (EI+) 320 (M+).
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[N:16][CH:15]=2)[CH:3]=1.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>CN(C=O)C>[CH3:11][C:9]1[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[N:16][CH:15]=3)[CH:3]=[C:2]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[N:7]2[N:8]=1
Reactant: Cc1cc2nc(NC(=O)c3ccc(C(F)(F)F)nc3)cc(Cl)n2n1
Reactant: C1COCCN1
Solvent: CN(C)C=O
Product: Cc1cc2nc(NC(=O)c3ccc(C(F)(F)F)nc3)cc(N3CCOCC3)n2n1
Temperature: 25 °C
Yield: 54.2 %

Procedure:
A solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-6-(trifluoromethyl)nicotinamide (12A, 81 mg, 0.228 mmol) and morpholine (67 mg, 0.761 mmol) in DMF (0.912 mL) was stirred at 100° C. for 90 min, then cooled to rt and maintained overnight. The mixture was filtered and the crude material recrystallized from hot methanol, providing the titled compound as a white solid (50.2 mg, 54%). 1H NMR (DMSO-d6) δ: 11.45 (s, 1H), 9.28 (d, 1H), 8.59-8.63 (m, 1H), 8.09 (d, J=8.1 Hz, 1H), 7.31 (s, 1H), 6.21 (s, 1H), 3.80-3.89 (m, 4H), 3.68-3.80 (m, 4H), 2.39 (s, 3H); ESI-MS: m/z 407.2 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[CH:5]=[CH:6][CH:7]=1.[Li]CCCC.[CH3:23][C:24](N(C)C)=[O:25].Cl>O1CCCC1.CCCCCC.O>[Si:11]([O:10][CH2:9][CH2:8][C:4]1[CH:3]=[C:2]([C:24](=[O:25])[CH3:23])[CH:7]=[CH:6][CH:5]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]
Reactant: CC(C)(C)[Si](C)(C)OCCc1cccc(Br)c1
Reactant: CC(=O)N(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: O
Product: CC(=O)c1cccc(CCO[Si](C)(C)C(C)(C)C)c1
Reaction time: 0.5 h

Procedure:
To a solution of 1.6 g of [2-(3-bromophenyl)ethoxy](tert-butyl)dimethylsilane in tetrahydrofuran (20 ml) was added n-BuLi in hexane (1.57M, 3.88 ml) at −70° C., then the reaction mixture was stirred at same temperature for 30 min. To the solution was added dimethylacetamide (1.42 ml) drop wise at the same temperature. The mixture was stirred for another 1 hour. To the reaction mixture were added water and 8 ml of 1N HCl under ice-cooling. The mixture was stirred for 1 hour, then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography with n-hexane and ethyl acetate (20/1–10/1) as an eluent to give 1-[3-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]ethanone (350 mg) as colorless oil.
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[CH:3]=[CH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11]([NH2:14])(=[O:13])=[O:12].[H][H]>[Pd].C(OCC)(=O)C>[F:16][C:2]([F:1])([F:15])[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11]([NH2:14])(=[O:13])=[O:12]
Reactant: [H][H]
Reactant: NS(=O)(=O)c1ccccc1C=CC(F)(F)F
Agent: [Pd]
Solvent: CCOC(C)=O
Product: NS(=O)(=O)c1ccccc1CCC(F)(F)F

Procedure:
A mixture of 50.2 g of 2-(3,3,3-trifluoro-1-propenyl)-phenylsulfonamide, 500 ml of ethyl acetate and 5 g of a 5% Pd/C catalyst is shaken for 1/2 hour at 20°-25° C. in a hydrogen atmosphere. The catalyst is then filtered off, the mixture is concentrated by evaporation, and the residue is crystallised from a mixture of methylene chloride and ether to thus yield 49.6 g of 2-(3,3,3-trifluoropropyl)phenylsulfonamide, m.p. 148°-149° C.
Reaction SMILES: Br[C:2]1C=C(Br)C=C(Br)C=1OS(C1C(C)=CC=CC=1)(=O)=O.[C:21]1(C)[C:22]([S:27]([Cl:30])(=[O:29])=[O:28])=[CH:23][CH:24]=[CH:25][CH:26]=1>>[C:25]1([CH3:2])[CH:26]=[CH:21][C:22]([S:27]([Cl:30])(=[O:28])=[O:29])=[CH:23][CH:24]=1
Reactant: Cc1ccccc1S(=O)(=O)Oc1c(Br)cc(Br)cc1Br
Reactant: Cc1ccccc1S(=O)(=O)Cl
Product: Cc1ccc(S(=O)(=O)Cl)cc1

Procedure:
In the same manner the o-toluenesulfonic acid-2,4,6-tribromophenyl ester can be obtained by using o-toluenesulfonyl chloride in the same molar amount instead of the para compound.
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]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[CH:24][C:25]2[CH2:31][CH2:30][CH2:29][NH:28][C:27](=[O:32])[C:26]=2[CH:33]=1.CC1(C)[C@]2(CS(O)(=O)=O)C(C[C@H]1CC2)=O>C(O)(C)C>[Cl:20][C:5]1[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])=[N:7][C:2]([NH:21][C:22]2[CH:23]=[CH:24][C:25]3[CH2:31][CH2:30][CH2:29][NH:28][C:27](=[O:32])[C:26]=3[CH:33]=2)=[N:3][CH:4]=1
Reactant: Nc1ccc2c(c1)C(=O)NCCC2
Reactant: CNC(=O)c1cccc(C)c1Nc1nc(Cl)ncc1Cl
Agent: CC1(C)[C@@H]2CC[C@@]1(CS(=O)(=O)O)C(=O)C2
Solvent: CC(C)O
Product: CNC(=O)c1cccc(C)c1Nc1nc(Nc2ccc3c(c2)C(=O)NCCC3)ncc1Cl
Yield: 17.3 %

Procedure:
Combined 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3,N-dimethyl-benzamide (100 mg, 0.321 mmol), 8-Amino-2,3,4,5-tetrahydro-benzo[c]azepin-1-one (69 mg, 0.392 mmol), DL-10-Camphorsulfonic acid (93 mg, 0.400 mmol) and isopropanol (4 mL) in a microwave tube. Microwaved reaction at 120° C. for 30 minutes. Evaporated off solvent and purified with normal phase chromatography to yield an off-white solid, 2-[5-Chloro-2-(1-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-ylamino)-pyrimidin-4-ylamino]-3,N-dimethyl-benzamide (25 mg, 17%). mp 259° C.; LCMS: m/z=451.36 (M+H+), 1H NMR (400 MHz, CD3OD) δ 8.02 (s, 1H), 7.69 (m, 1H), 7.58 (s, 1H), 7.42 (m, 2H), 7.37 (m, 1H), 7.30 (m, 1H), 6.97 (d, 1H, J=8.3 Hz), 4.24 (m, 1H), 3.50 (m, 1H), 3.15 (m, 1H), 3.02 (m, 2H), 2.82 (s, 3H), 2.73 (m, 2H), 2.24 (s, 3H), 1.97 (m, 2H).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][N:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:7]=1)#[N:2].C(O[CH:17](OCC)[N:18]([CH3:20])[CH3:19])C>>[C:1]([C:3]1[CH:4]=[N:5][N:6]([C:8](=[CH:17][N:18]([CH3:20])[CH3:19])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:7]=1)#[N:2]
Reactant: CCOC(OCC)N(C)C
Reactant: CCOC(=O)Cn1cc(C#N)cn1
Product: CCOC(=O)C(=CN(C)C)n1cc(C#N)cn1
Yield: 88.5 %

Procedure:
Combined ethyl 2-(4-cyano-1H-pyrazol-1-yl)acetate (0.427 g, 2.383 mmol) with 1,1-diethoxy-N,N-dimethylmethanamine (1.403 g, 9.53 mmol) and heated in a closed vial at 100° C. for 2.5 h. The mixture was concentrated in vacuo and purified using flash column chromatography on NH silica gel (30 g SiO2, EtOAc in heptane, 10-50% gradient) to give the title compound (0.4942 g, 89% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.12 (t, 3H) 1.91-2.43 (m, 3H) 2.70-3.29 (m, 3H) 4.03 (q, J=7.07 Hz, 2H) 7.59 (s, 1H) 8.14 (s, 1H) 8.56 (s, 1H). MS m/z [M+H]+ 235
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([CH2:7][O:8][C@H:9]([C@H:11]([OH:20])[C@H:12]([CH:18]=[CH2:19])[CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH3:10])=[CH:5][CH:4]=1.[H-].[Na+].[CH3:25][C:26]1[CH:31]=CC(S(OCC(C)C)(=O)=O)=C[CH:27]=1>CN(C=O)C>[CH2:25]([O:20][C@H:11]([C@H:12]([CH:18]=[CH2:19])[CH2:13][CH2:14][CH:15]([CH3:16])[CH3:17])[C@@H:9]([O:8][CH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:22][CH:21]=1)[CH3:10])[CH:26]([CH3:31])[CH3:27]
Reactant: C=C[C@H](CCC(C)C)[C@@H](O)[C@H](C)OCc1ccc(OC)cc1
Reactant: Cc1ccc(S(=O)(=O)OCC(C)C)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=C[C@H](CCC(C)C)[C@@H](OCC(C)C)[C@H](C)OCc1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 86.6 %

Procedure:
A solution of (2S,3R,4S)-2-((4-methoxybenzyl)oxy)-7-methyl-4-vinyloctan-3-ol (2.0 g, 6.53 mmol) in anhydrous DMF (15 mL) was added at room temperature to a solution of NaH (0.326 g, 8.16 mmol, 60% dispersion in mineral oil) in anhydrous DMF (6.0 mL). The reaction was stirred for 15 min at room temperature, then isobutyl 4-methylbenzenesulfonate (1.66 mL, 8.16 mmol) was added at room temperature and the reaction was heated at 50° C. and stirred for 1 h. The reaction was cooled down to room temperature and NaH (0.261 g, 6.53 mmol) followed by isobutyl 4-methylbenzenesulfonate (1.33 mL, 6.53 mmol) were added and heating continued for 2 h at 50° C., after which the reaction was again cooled down to room temperature and a third batch of NaH (0.131 g, 3.27 mmol) and isobutyl 4-methylbenzenesulfonate (0.67 mL, 3.27 mmol) were added and the reaction was heated at 50° C. for 7 h. The reaction mixture was quenched with saturated NH4Cl and the phases were separated. The aqueous phase was extracted with Et2O, and the combined organic phases were washed with brine, dried over MgSO4, concentrated, and purified by column chromatography on SiO2 (gradient, hexanes/ethyl acetate) to furnish the title product as a colorless oil (2.05 g, 87%): 1H NMR (400 MHz, CDCl3) δ 7.29-7.21 (m, 2H), 6.90-6.83 (m, 2H), 5.61-5.49 (m, 1H), 5.04-4.89 (m, 2H), 4.53-4.33 (m, 2H), 3.80 (s, 3H), 3.64-3.51 (m, 2H), 3.28-3.16 (m, 2H), 2.15-2.02 (m, 1H), 1.90-1.77 (m, 1H), 1.76-1.60 (m, 1H), 1.54-1.41 (m, 1H), 1.28-1.11 (m, 2H), 1.17 (d, J=6.3 Hz, 3H), 1.08-0.96 (m, 1H), 0.95-0.88 (m, 6H), 0.86 (d, J=6.4 Hz, 3H), 0.85 (d, J=6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 158.97, 140.43, 131.09, 129.06, 115.66, 113.67, 84.26, 79.58, 76.41, 70.05, 55.26, 47.38, 36.46, 29.13, 28.21, 27.85, 22.91, 22.47, 19.66, 19.55, 14.25; ESIMS m/z 385.4 ([M+Na]+).
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:25]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:24]([CH2:34][O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:23][CH:10]1OC(=O)C1C=CC([N+]([O-])=O)=CC=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[N:52]([C:55]1[N:63]=[C:62]([F:64])[N:61]=[C:60]2[C:56]=1[NH:57][CH:58]=[N:59]2)=[N+:53]=[N-:54]>ClCCCl.ClCCl>[N:52]([C:55]1[N:63]=[C:62]([F:64])[N:61]=[C:60]2[C:56]=1[N:57]=[CH:58][N:59]2[C@@H:10]1[O:23][C@H:24]([CH2:34][O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@@H:25]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:9]1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[N+:53]=[N-:54]
Reactant: O=C(OC1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1)c1ccc([N+](=O)[O-])cc1
Reactant: [N-]=[N+]=Nc1nc(F)nc2nc[nH]c12
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: ClCCCl
Product: [N-]=[N+]=Nc1nc(F)nc2c1ncn2[C@@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 24.6 %

Procedure:
A solution of 2,3,5-tri-O-benzyl-1-α-D-arabinofuranosylchloride (freshly prepared from 1.9 g of 2,3,5-tri-O-benzyl-1-O-p-nitrobenzoyl-D-arabinofuranose), N,N-diisopropylethylamine (0.58 mL) and 6-azido-2-fluoropurine (0.50 g) in 10 mL of anhydrous 1,2-dichloroethane was heated at reflux overnight. Additional N,N-diisopropylethylamine (0.26 mL) was added and heating was continued for an additional 24 hours. The mixture was cooled to ambient temperature and diluted with dichloromethane (60 mL) and washed sequentially with 10% aqueous sodium hydroxide (NaOH), water, 1N phosphoric acid (H3PO4), saturated NaCl and then dried over MgSO4 along with decolorizing carbon. The dried solution was filtered through celite and concentrated in vacuo. The residue was purified by silica gel chromatography with gradient elution from 3:1 Hexane:ethyl acetate to 100% ethyl acetate to obtain 0.40 g of the title compound as a colorless oil; IR (neat) 3031, 2922, 2867, 2126, 1608 cm-1 ; 1H NMR (DMSO-d6, 360 MHz) δ3.65-3.75 (m, 2H), 4.16 (q, J=5 Hz, 1H), 4.22 (d, J=11.8 Hz), 4.42 (t, J=5.5 Hz, 1H), 4.47 (d, J=11.8 Hz, 1H), 4.51 (s, 2H), 4.58 (t, J=5.5 Hz, 1H), 4.62 (d, J=12.0 Hz, 1H), 4.68 (d, J=12.0 Hz, 1H), 6.41 (d, J=5.5 Hz, 1H), 6.9-6.95 (m, 2H) 7.1-7.2 (m, 3H), 7.25-7.4 (m, 10H), 8.48 (s, 1H); UV (MeOH) λmax, 286 nm; MS (EI+, m/z) 582 (M+H)+.
Reaction SMILES: [CH2:1]([O:8][NH:9][C:10]1[N:15]=[C:14]([NH:16][CH:17]=[O:18])[N:13]=[C:12]([Cl:19])[C:11]=1[NH:20][CH:21]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(OC(OCC)OCC)(=O)C>[CH2:1]([O:8][N:9]1[CH:21]=[N:20][C:11]2[C:10]1=[N:15][C:14]([NH:16][CH:17]=[O:18])=[N:13][C:12]=2[Cl:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=CNc1nc(Cl)c(NC=O)c(NOCc2ccccc2)n1
Agent: CCOC(OCC)OC(C)=O
Product: O=CNc1nc(Cl)c2ncn(OCc3ccccc3)c2n1
Temperature: 20 °C
Reaction time: 1 h
Yield: 61.8 %

Procedure:
6-Benzyloxyamino-4-chloro-2,5-diformamidopyrimidine (1.2g, 3.73mmol) and diethoxymethyl acetate (20ml) was stirred at 120° C. for 2.5 hours, cooled and evaporated under reduced pressure. The residue in methanol (20ml) and concentrated ammonia solution (2ml) was stirred at 20° C. for 1 hour, the solvent removed under reduced pressure and the residue co-evaporated with methanol. Column chromatography on silica gel (eluted with chloroform-ethanol, 100:1) afforded the title compound (700mg, 62%). IR: υmax (KBr) 3119, 1702, 1611, 1577, 1505, 1440cm-1 ; 1H NMR: δH [(CD3)2SO], 5.44 (2H, s, CH2Ph), 7.45 (5H, m, Ph), 8.54 (1H, s, H-8), 9.34 (1H, s, CHO), 11.30 (1H, br.s, D2O exchangeable, NH). Found: C, 49.99; H, 3.37; N, 22.43%, m/e 303.0523. C13H10N5O2Cl + 0.5 H2O requires: C, 49.92; H, 3.55; N, 22.40%, m/e 303.0520.
Reaction SMILES: [C:1](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C@H:22]2[N:29]3[C:25]([S:26][C:27]([C:33]([N:35]4[CH2:49][C@H:48]([F:50])[CH2:47][C@H:36]4[C:37]([N:39]4[CH2:46][C:43]5([CH2:45][CH2:44]5)[NH:42][CH2:41][CH2:40]4)=[O:38])=[O:34])=[C:28]3[CH:30]([CH3:32])[CH3:31])=[N:24][C@:23]2([C:52]2[CH:53]=[N:54][C:55]([Cl:58])=[CH:56][CH:57]=2)[CH3:51])=[CH:18][C:17]=1[F:59].C=O.C(=O)(O)[O-].[Na+]>O1CCOCC1>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C@H:22]2[N:29]3[C:25]([S:26][C:27]([C:33]([N:35]4[CH2:49][C@H:48]([F:50])[CH2:47][C@H:36]4[C:37]([N:39]4[CH2:46][C:43]5([CH2:44][CH2:45]5)[N:42]([CH3:1])[CH2:41][CH2:40]4)=[O:38])=[O:34])=[C:28]3[CH:30]([CH3:31])[CH3:32])=[N:24][C@:23]2([C:52]2[CH:53]=[N:54][C:55]([Cl:58])=[CH:56][CH:57]=2)[CH3:51])=[CH:18][C:17]=1[F:59]
Reactant: CC(C)C1=C(C(=O)N2C[C@H](F)C[C@H]2C(=O)N2CCNC3(CC3)C2)SC2=N[C@@](C)(c3ccc(Cl)nc3)[C@@H](c3ccc(Cl)c(F)c3)N21
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Product: CC(C)C1=C(C(=O)N2C[C@H](F)C[C@H]2C(=O)N2CCN(C)C3(CC3)C2)SC2=N[C@@](C)(c3ccc(Cl)nc3)[C@@H](c3ccc(Cl)c(F)c3)N21
Reaction time: 17 h
Yield: 89.1 %

Procedure:
Sodium triacetoxyborohydride (267 mg, 1.26 mmol) was added to a 1,4-dioxane (10 ml) solution of the compound (340 mg, 0.503 mmol) obtained in Step 2 of Example 1 and 37% aqueous paraformaldehyde solution (0.41 ml, 5.05 mmol) at room temperature and the resulting mixture was stirred for 17 hours. Saturated aqueous sodium bicarbonate solution was added, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate and the solvent was concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography [chloroform:methanol=50:1 (v/v)) to give the title compound (309 mg, 89%) as a colorless solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:24])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:16][CH2:17][CH2:18][CH:19]=O)=[O:15])=[CH:11][C:10]=1[N+:21]([O-:23])=[O:22].[CH3:25][N:26]([CH3:33])[CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:24])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:16][CH2:17][CH2:18][CH2:19][N:30]2[CH2:31][CH2:32][CH:27]([N:26]([CH3:33])[CH3:25])[CH2:28][CH2:29]2)=[O:15])=[CH:11][C:10]=1[N+:21]([O-:23])=[O:22]
Reactant: CN(C)C1CCNCC1
Reactant: O=CCCNC(=O)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Product: CN(C)C1CCN(CCCNC(=O)c2cc([N+](=O)[O-])c(Sc3c(Cl)cncc3Cl)s2)CC1

Procedure:
Prepared according to the procedure described for step D of example 223 from 5-((3,5-dichloropyridin-4-yl)thio)-4-nitro-N-(3-oxopropyl)thiophene-2-carboxamide (100 mg, 0.23 mmol) and N,N-dimethylpiperidin-4-amine (6.0 mg, 0.28 mmol). The title compound was afforded as a solid (30.0 mg, 25% yield). 1H NMR (400 MHz, d6-DMSO) δ: 9.02 (2H, s), 8.88 (1H, m), 8.46 (1H, s), 3.23 (2H, m), 2.93 (2H, m), 2.31 (9H, m), 1.91 (2H, m), 1.79 (2H, m), 1.66 (2H, m), 1.41 (2H, m). MS m/z: 518.16, 520.15 [M+H]+.
Reaction SMILES: [ClH:1].C[O:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][C@H:8]([N:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18])[C@@H:9]2[CH3:14].Br>CO>[ClH:1].[OH:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][C@H:8]([N:15]([CH2:16][CH2:17][CH3:18])[CH2:19][CH2:20][CH3:21])[C@@H:9]2[CH3:14]
Reactant: CCCN(CCC)[C@H]1CCc2c(OC)cccc2[C@H]1C
Agent: Br
Agent: Cl
Solvent: CO
Product: CCCN(CCC)[C@H]1CCc2c(O)cccc2[C@H]1C
Yield: 72.7 %

Procedure:
(-)-cis-5-Methoxy-1-methyl-2-(di-n-propylamino)tetralin hydrochloride (0.37 g, 0.0012 mol) was treated with 48% HBr (15 ml) as described above to give (-)-cis-5-hydroxy-1-methyl-2-(di-n-propylamino)tetralin hydrochloride (0.26 g, 55%) m.p. 228°-229° C., [α]D22 =-50.1 (c=1.1, CH3OH).