Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:16][C:15]2[C:11](=[C:12]([CH3:25])[N:13]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:14]=2)[C:10](=O)[CH2:9]1.[C:27]([NH:30][NH2:31])([NH2:29])=[NH:28].Cl.Cl.O>C(O)C>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:16][C:15]2[C:11](=[C:12]([CH3:25])[N:13]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:14]=2)[C:10](=[N:31][NH:30][C:27]([NH2:29])=[NH:28])[CH2:9]1
Reactant: N=C(N)NN
Reactant: Cc1c2c(nn1CCc1ccccc1)CC(c1ccccc1Cl)CC2=O
Agent: Cl
Solvent: CCO
Solvent: O
Product: Cc1c2c(nn1CCc1ccccc1)CC(c1ccccc1Cl)CC2=NNC(=N)N
Yield: 135.6 %

Procedure:
A mixture of 6-(2-chlorophenyl)-3-methyl-2-(2-phenylethyl)-4,5,6,7-tetrahydroindazol-4-one (0.20 g), aminoguanidine hydrochloride (0.073 g), concentrated hydrochloric acid (0.14 ml), water (0.14 ml) and ethanol (15 ml) was refluxed for 12 hours. Under reduced pressure, the solvent was evaporated, and the resulting crystals were recrystallized from ethanol to give 6-(2-chlorophenyl)-4-guanidinoimino-3-methyl-2-(2-phenylethyl)-4,5,6,7-tetrahydroindazole hydrochloride (Compound 152) (0.17 g) as colorless crystals.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]([F:14])([F:13])[C:10]([OH:12])=[O:11].FC(F)(F)C(O)=O.[Cl:22][C:23]1[CH:24]=[N:25][C:26]2[NH:27][C:28]3[CH:29]=[N:30][CH:31]=[C:32]([CH:54]=3)[CH2:33][CH2:34][C:35]3[CH:43]=[C:39]([NH:40][C:41]=1[N:42]=2)[CH:38]=[CH:37][C:36]=3[NH:44][C:45](=[O:53])[CH2:46][CH:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1.[CH3:55][C:56]([CH3:61])([CH3:60])[C:57](Cl)=[O:58]>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]([F:14])([F:13])[C:10]([OH:12])=[O:11].[Cl:22][C:23]1[CH:24]=[N:25][C:26]2[NH:27][C:28]3[CH:29]=[N:30][CH:31]=[C:32]([CH:54]=3)[CH2:33][CH2:34][C:35]3[CH:43]=[C:39]([NH:40][C:41]=1[N:42]=2)[CH:38]=[CH:37][C:36]=3[NH:44][C:45](=[O:53])[CH2:46][CH:47]1[CH2:52][CH2:51][N:50]([C:57](=[O:58])[C:56]([CH3:61])([CH3:60])[CH3:55])[CH2:49][CH2:48]1
Reactant: O=C(CC1CCNCC1)Nc1ccc2cc1CCc1cncc(c1)Nc1ncc(Cl)c(n1)N2
Reactant: CC(C)(C)C(=O)Cl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)C(=O)N1CCC(CC(=O)Nc2ccc3cc2CCc2cncc(c2)Nc2ncc(Cl)c(n2)N3)CC1
Yield: 32 %

Procedure:
The desired compound was prepared according to the procedure of Example A20, using N-[6-chloro-2,4,8,18,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaen-12-yl]-2-piperidin-4-ylacetamide tris(trifluoroacetate) and 2,2-dimethylpropanoyl chloride as starting materials in 32% yield. LCMS for C29H35ClN7O2 (M+H)+: m/z=548.2.
Reaction SMILES: [CH:1]([N-]C(C)C)(C)[CH3:2].[Li+].[I:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][C:17]([OH:19])=[O:18].ICC>C1COCC1>[I:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH:16]([CH2:1][CH3:2])[C:17]([OH:19])=[O:18]
Reactant: CC(C)[N-]C(C)C
Reactant: O=C(O)Cc1ccccc1I
Agent: [Li+]
Solvent: CCI
Solvent: C1CCOC1
Product: CCC(C(=O)O)c1ccccc1I
Temperature: 0 °C
Reaction time: 4 h

Procedure:
Lithium diisopropylamide solution (2.0 M in THF/heptane/ethylbenzene, 3.82 mL, 7.63 mmol) was added to dry THF (10 mL) under an atmosphere of nitrogen and cooled to 0° C. A solution of 2-(2-iodophenyl)acetic acid (500 mg, 1.91 mmol) in dry THF (15 mL) was then added dropwise. This solution was stirred for 40 minutes at 0° C. before the addition of iodoethane (0.92 mL, 11 mmol). The solution was returned to room temperature and stirred for 4 hours. The resulting mixture was quenched with the addition of H2O (10 mL) and then 2 M HCl (20 mL). The aqueous layer was extracted with EtOAc (3×30 mL), the organic layers were combined and washed with brine, dried over MgSO4 and the solvent was evaporated under reduced pressure. The residue was adsorbed onto silica gel and purified using column chromatography (Biotage Isolera, SiO2 cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.) to give the title compound I1 as a pale yellow oil (479 mg, 87%); 1H NMR (400 MHz, d6-DMSO) δ 12.49 (s, 1H), 7.88 (dd, J=7.9, 1.2 Hz, 1H), 7.39 (td, J=7.6, 1.2 Hz, 1H), 7.32 (dd, J=7.8, 1.7 Hz, 1H), 7.01 (J m, 1H), 3.77 (t, J=7.5 Hz, 1H), 1.98-1.86 (m, 1H), 1.73-1.60 (m, 1H), 0.85 (t, J=7.3 Hz, 3H).
Reaction SMILES: [C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:14][C:15]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:16]=1[C:17](Cl)=[O:18]>O1CCCC1>[F:14][C:15]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:16]=1[C:17]([N:11]1[CH2:12][CH2:13][N:8]([CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][CH2:10]1)=[O:18]
Reactant: O=C(Cl)c1ccc(F)cc1F
Reactant: c1ccc(CN2CCNCC2)cc1
Solvent: C1CCOC1
Product: O=C(c1ccc(F)cc1F)N1CCN(Cc2ccccc2)CC1
Yield: 87.8 %

Procedure:
To a stirred and cooled mixture (10° C.) of 64 parts of 1-(phenyl-methyl)piperazine and 360 parts of tetrahydrofuran were added during 20 minutes 32.5 parts of 2,4-difluorobenzoyl chloride. Upon complete addition, stirring was continued until room temperature. The formed salt was filtered off and the filtrate was evaporated in vacuo. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated, yielding 50 parts (87.8%) of 1-(2,4-difluorobenzoyl)-4-(phenylmethyl)-piperazine as a residue (int. 5).
Reaction SMILES: [Cl:1][C:2]1[C:15]2[C:14](=O)[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[S:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.ClC1C=CC=C(Cl)C=1C#[N:21].C1(S)C=CC=CC=1>>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([S:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:15]=1[C:14]#[N:21]
Reactant: O=c1c2ccccc2sc2cccc(Cl)c12
Reactant: N#Cc1c(Cl)cccc1Cl
Agent: Sc1ccccc1
Product: N#Cc1c(Cl)cccc1Sc1ccccc1

Procedure:
U.S. Pat. No. 3,711,513 teaches the preparation of 1-chloro-thioxanthone by reacting 2,6-dichloro-benzonitrile with an alkali metal salt of thiophenol to obtain 2-chloro-6-phenylthio-benzonitrile, which is reacted with polyphosphoric acid to give 1-chloro-9-imino-thioxanthene, this latter product being hydrolysed to 1-chloro-thioxanthone.
Reaction SMILES: [CH3:1][C:2]1([CH2:7][CH2:8][CH2:9][CH2:10][N:11]2[CH:15]=[CH:14][C:13]([NH2:16])=[N:12]2)[O:6]CCO1.[Cl:17][C:18]1[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=1/[CH:25]=[CH:26]/[C:27](O)=[O:28]>>[Cl:17][C:18]1[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=1/[CH:25]=[CH:26]/[C:27]([NH:16][C:13]1[CH:14]=[CH:15][N:11]([CH2:10][CH2:9][CH2:8][CH2:7][C:2](=[O:6])[CH3:1])[N:12]=1)=[O:28]
Reactant: O=C(O)/C=C/c1cccc(Cl)c1Cl
Reactant: CC1(CCCCn2ccc(N)n2)OCCO1
Product: CC(=O)CCCCn1ccc(NC(=O)/C=C/c2cccc(Cl)c2Cl)n1

Procedure:
Following general procedure B followed by either C or D, starting from 1-[4-(2-methyl-[1,3]dioxolan-2-yl)-butyl]-1H-pyrazol-3-ylamine and (E)-3-(2,3-dichloro-phenyl)-acrylic acid.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[CH:2].[ClH:22]>C(OCC)(=O)C>[ClH:22].[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]2)=[CH:5][CH:4]=1)#[CH:2]
Reactant: C#Cc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2)cc1
Agent: Cl
Solvent: CCOC(C)=O
Product: C#Cc1ccc(C2CCNCC2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 81 %

Procedure:
Into a 100-mL round-bottom flask, was placed a solution of tert-butyl 4-(4-ethynylphenyl)piperidine-1-carboxylate (compound 76.3, 1.0 g, 3.5 mmol) in ethyl acetate (20 mL). Hydrogen chloride (g) was introduced by bubbling through the solution and the resulting solution was stirred for 1 hour at room temperature. The solids that formed were collected by filtration and washed with hexanes (3×10 mL) to yield the title compound as a brown solid (630 mg, 81%).
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[O:14][N:13]=[C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:11]=1.[CH3:22][NH2:23]>CCOCC.O>[C:15]1([C:12]2[N:11]=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[C:3]([NH:23][CH3:22])=[O:2])[O:14][N:13]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)c1ccccc1-c1nc(-c2ccccc2)no1
Reactant: CN
Solvent: O
Solvent: CCOCC
Product: CNC(=O)c1ccccc1-c1nc(-c2ccccc2)no1
Reaction time: 19 h

Procedure:
A solution of 6.16 g. (0.022 mole) o-(3-phenyl-1,2,4-oxadiazol-5-yl)-benzoic acid methyl ester in 150 milliliters ether is treated with 150 milliliters 40 percent methyl amine in water. The resulting two-phase system is stirred vigorously for 19 hours. The ether is evaporated, and the resulting mixture extracted with methylene chloride. The organic phase is washed with water and then brine, dried over anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The resulting solid is triturated with ether and filtered to give o-(3-phenyl-1,2,4-oxadiazol-5-yl)-N-methyl benzamide, m.p. 145°-146° C.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N:12]3[CH2:16][CH2:15][CH2:14][C:13]3=[O:17])[CH:10]=2)[N:5]=[C:4]([CH3:18])[CH:3]=1.[C:19]1([CH:25]2[CH2:29][CH2:28][NH:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(OCCO)C.[OH-].[Na+]>[CH3:18][C:4]1[CH:3]=[C:2]([N:27]2[CH2:28][CH2:29][CH:25]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:26]2)[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N:12]3[CH2:16][CH2:15][CH2:14][C:13]3=[O:17])[CH:10]=2)[N:5]=1
Reactant: c1ccc(C2CCNC2)cc1
Reactant: Cc1cc(Cl)c2cc(N3CCCC3=O)ccc2n1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCCO
Product: Cc1cc(N2CCC(c3ccccc3)C2)c2cc(N3CCCC3=O)ccc2n1
Temperature: 250 °C
Yield: 28.1 %

Procedure:
A mixture of 1-(4-chloro-2-methylquinolin-6-yl)pyrrolidin-2-one (0.2 g; see Preparation 6 above) and 3-phenylpyrrolidine (0.282 g) in 2-ethoxyethanol was heated in a microwave at 250° C. for 20 minutes. The reaction mixture was diluted with 1 N sodium hydroxide and extracted with ethyl acetate, washed with water, dried (MgSO4), filtered and evaporated. Trituration from ether gave the title compound as a white powder (0.08 g).
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[N:13]=[CH:12][C:11]2[N:10]([CH2:14][C:15]([NH:17][CH2:18][CH:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[O:16])[CH2:9][C@@H:8]3[CH2:25][O:26][CH2:27][CH2:28][N:7]3[C:6]=2[N:5]=1.CI.[CH3:31]COC(C)=O>CN(C=O)C>[Cl:3][C:4]1[N:13]=[CH:12][C:11]2[N:10]([CH2:14][C:15]([N:17]([CH3:31])[CH2:18][CH:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)=[O:16])[CH2:9][C@@H:8]3[CH2:25][O:26][CH2:27][CH2:28][N:7]3[C:6]=2[N:5]=1
Reactant: O=C(CN1C[C@@H]2COCCN2c2nc(Cl)ncc21)NCC1CCOCC1
Reactant: CCOC(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: CN(C)C=O
Product: CN(CC1CCOCC1)C(=O)CN1C[C@@H]2COCCN2c2nc(Cl)ncc21
Yield: 70.4 %

Procedure:
Sodium hydride (60% in oil) (12.57 mg, 0.314 mmol) was added to a suspension of (R)-2-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide (PREPARATION x26, 100 mg, 0.262 mmol) in DMF (1 mL) at 0° C. The resultant mixture was stirred at room temperature for 30 minutes. Methyl iodide (0.021 mL, 0.340 mmol) was added to the reaction mixture at room temperature, and the resultant mixture was stirred at room temperature for 15 minutes. After addition of EtOAc, the resultant mixture was washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was washed with EtOAc to afford the title compound as a white solid (73 mg, 70.4%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04-1.38 (m, 2 H), 1.48 (d, J=11.12 Hz, 2 H), 1.75-1.99 (m, 1 H), 2.80-3.01 (m, 4 H), 3.09-3.31 (m, 7 H), 3.40-3.64 (m, 2 H), 3.79-4.06 (m, 5 H), 4.17-4.27 (m, 1 H), 4.34-4.44 (m, 1 H), 7.12-7.29 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C18H26ClN5O3, 396.18; found 396.3.
Reaction SMILES: Cl.[CH:2]1([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH:16][C:17]2[CH:25]=[CH:24][C:20]([C:21](Cl)=[O:22])=[CH:19][CH:18]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[C:26]1([S:32]([NH2:35])(=[O:34])=[O:33])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[Na]>CC(N(C)C)=O>[CH:2]1([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH:16][C:17]2[CH:25]=[CH:24][C:20]([C:21]([NH:35][S:32]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)(=[O:34])=[O:33])=[O:22])=[CH:19][CH:18]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: O=C(Cl)c1ccc(NCCCCCCCCC2CCCCC2)cc1
Reactant: NS(=O)(=O)c1ccccc1
Agent: Cl
Agent: [Na]
Solvent: CC(=O)N(C)C
Product: O=C(NS(=O)(=O)c1ccccc1)c1ccc(NCCCCCCCCC2CCCCC2)cc1
Reaction time: 0.5 h

Procedure:
To the resulting oily residue of p-(8-cyclohexyloctyl)aminobenzoyl chloride hydrochloride is added, in one portion, the previously prepared mixture of sodium benzenesulfonamide in dimethylacetamide. The mixture is stirred for 30 minutes, without cooling, and is then filtered through a bed of diatomaceous earth. The filtrate is poured into 2 l. of water, and 250 ml. of saturated sodium chloride solution is added to coagulate the precipitate. The mixture is filtered and the product is washed with water and partially air dried. The product is dissolved in methylene chloride, the mixture is filtered through diatomaceous earth, and brine is added to break the emulsion. The layers are separated, the organic phase is dried over anhydrous sodium sulfate and filtered through a bed of 300 g. of hydrous magnesium silicate. The product is eluted with an additional 3 l. of methylene chloride. The first approx. 1 l. of filtrate is set aside and the remainder is evaporated to dryness. The residue is crystallized three times from toluene to yield the product.
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[CH2:7][C:6]([CH2:15][CH:16]=O)([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[CH2:5][CH2:4][O:3]1.[CH3:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23][NH2:24].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:1][C:2]1([CH3:18])[CH2:7][C:6]([CH2:15][CH2:16][NH:24][CH2:23][C:22]2[CH:25]=[CH:26][CH:27]=[C:20]([CH3:19])[CH:21]=2)([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[CH2:5][CH2:4][O:3]1
Reactant: Cc1cccc(CN)c1
Reactant: Cc1ccc(C2(CC=O)CCOC(C)(C)C2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: Cc1ccc(C2(CCNCc3cccc(C)c3)CCOC(C)(C)C2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 2-[2,2-dimethyl-4-(4-methylphenyl)oxan-4-yl]acetaldehyde (61.6 mg, 0.25 mmol), 3-methylbenzylamine (63 μl, 0.5 mmol) and acetic acid (50 μl, 8.6 mmol) in CH2Cl2 (3 ml) was stirred at rt for 1 h before it adding sodium triacetoxyborohydride (106 mg, 0.50 mmol). The resulting mixture was stirred at rt for 18 h. The mix was concentrated and dissolved in MeOH and purified by HPLC to give {2-[2,2-dimethyl-4-(4-methylphenyl)oxan-4-yl]ethyl}[(3-methylphenyl)methyl]amine as a white solid (35 mg, 40%, m/z: 352.3 [M+H]+ observed).
Reaction SMILES: [C:1]1(=[O:8])[CH2:6][CH2:5][CH2:4][C:3](=O)[CH2:2]1.[NH2:9][CH:10]=[C:11]([CH3:14])[CH:12]=O.C(N(CC)CC)C>Cl.C([O-])(=O)C.[NH2+]1CCCCC1>[CH3:14][C:11]1[CH:10]=[N:9][C:3]2[CH2:4][CH2:5][CH2:6][C:1](=[O:8])[C:2]=2[CH:12]=1
Reactant: O=C1CCCC(=O)C1
Reactant: CC(C=O)=CN
Agent: C1CC[NH2+]CC1
Agent: CC(=O)[O-]
Agent: Cl
Solvent: CCN(CC)CC
Product: Cc1cnc2c(c1)C(=O)CCC2
Temperature: 120 °C
Reaction time: 24 h
Yield: 52.7 %

Procedure:
A mixture of cyclohexane-1,3-dione (22.4 g., 0.2 mol.), 3-amino-2-methylacrolein (17 g., 0.2 mol.), triethylamine (10 ml.) and piperidinium acetate (0.25 g.) was heated with stirring in an oil bath at 120° C for 24 hours. The cooled reaction mixture was dissolved in 2N HCl (50 ml.) and extracted with ethyl acetate (3 × 50 ml.) and the organic extracts discarded. The aqueous solution was adjusted to pH 10 with sodium carbonate and extracted with chloroform (3 × 50 ml.). The combined extracts were dried (MgSO4) and the solvent removed in vacuo. The residual oil was distilled to give the title compound as a colorless oil (17 g., 52%) b.p. 79°/0.2 mm Hg which solidified.
Reaction SMILES: [P:1]([O:13][CH2:14][C:15]([CH3:20])([CH3:19])[CH2:16][CH2:17][OH:18])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:22].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[C:9]([O:8][P:1]([O:13][CH2:14][C:15]([CH3:20])([CH3:19])[CH2:16][C:17]([OH:22])=[O:18])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])([CH3:10])([CH3:11])[CH3:12]
Reactant: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Reactant: CC(C)(CCO)COP(=O)(OC(C)(C)C)OC(C)(C)C
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: c1cc[nH+]cc1
Solvent: CN(C)C=O
Product: CC(C)(COP(=O)(OC(C)(C)C)OC(C)(C)C)CC(=O)O
Reaction time: 16 h
Yield: 58.4 %

Procedure:
To a solution of the product from Example 10C (0.235 g, 0.76 mmol) in DMF (7.6 mL) at room temperature was added pyridinium dichromate (1.71 g), and the mixture was stirred for 16 hours. 10% citric acid was added and the reaction mixture was extracted twice with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with a gradient starting with chloroform and ending with 5% methanol in chloroform, to give the title compound (0.144 g, 60%).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C@@H:7]2[O:19][C@H:18]([CH2:20][O:21]C(=O)C)[C@@H:13]([O:14]C(=O)C)[C@H:8]2[O:9]C(=O)C)[C:5]2[CH:25]=[CH:26][CH:27]=[CH:28][C:4]=2[N:3]=1.C([O:32][CH2:33][CH2:34][CH2:35][CH2:36][O:37][C:38]1[CH:39]=[C:40]([CH:43]=[C:44]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH:45]=1)[CH:41]=O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>O1CCCC1>[OH:32][CH2:33][CH2:34][CH2:35][CH2:36][O:37][C:38]1[CH:39]=[C:40]([CH:43]=[C:44]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH:45]=1)[CH2:41][NH:1][C:2]1[N:6]([C@@H:7]2[O:19][C@H:18]([CH2:20][OH:21])[C@@H:13]([OH:14])[C@H:8]2[OH:9])[C:5]2[CH:25]=[CH:26][CH:27]=[CH:28][C:4]=2[N:3]=1
Reactant: CC(=O)OCCCCOc1cc(C=O)cc(-c2ccccc2)c1
Reactant: CC(=O)OC[C@H]1O[C@@H](n2c(N)nc3ccccc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: OCCCCOc1cc(CNc2nc3ccccc3n2[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)cc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 13 h
Yield: 30.1 %

Procedure:
2-Amino-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-benzimidazole (0.20 g) and 3-(4-acetoxybutoxy)-5-phenylbenzaldehyde (0.19 g) were suspended in tetrahydrofuran (3 mL), and the mixture was stirred at room temperature for 13 hours. To the reaction mixture was added sodium triacetoxyborohydride (0.21 g), and the mixture was stirred at room temperature for 24 hours. After adding water to the reaction mixture, the mixture was concentrated under reduced pressure. The obtained residue was dissolved in methanol (2 mL). To the reaction mixture was added 5 mol/L aqueous sodium hydroxide solution (0.5 mL), and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added acetic acid (1 mL), and the mixture was concentrated under reduced pressure. The obtained residue was purified by preparative reverse phase column chromatography (Shiseido CAPSELL PAC C18UG80, 5 μm, 20×50 mm, flow rate 30 mL/minutes linear gradient, water/methanol=70/30-10/90) to give the title compound (0.08 g).
Reaction SMILES: N[C:2]1[C:3]2[N:4]([N:9]=[C:10]([S:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:11]=2)[C:5]([Cl:8])=[CH:6][CH:7]=1.C(O)(=O)C.N(OC(C)(C)C)=O>O1CCCC1>[CH2:13]([S:12][C:10]1[N:11]=[C:3]2[CH:2]=[CH:7][CH:6]=[C:5]([Cl:8])[N:4]2[N:9]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: Nc1ccc(Cl)n2nc(SCc3ccccc3)nc12
Agent: CC(C)(C)ON=O
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: Clc1cccc2nc(SCc3ccccc3)nn12

Procedure:
A solution of 8-amino-2-benzylthio-5-chloro[1,2,4]triazolo[1,5-a]pyridine (9.0 g, 0.031 mol) and acetic acid (2.0 g, 0.033 mol) in tetrahydrofuran (100 mL) was added dropwise with stirring over 30 min to a solution of t-butyl nitrite (6.4 g, i0.062 mol) in tetrahydrofuran (500 mL) at 50°-55° C. and allowed to react another 15 minutes after the addition was complete. The volatiles were removed by evaporation under reduced pressure and the residue obtained was chromatographed on silica gel eluting with a gradient of 5-15 percent ethyl acetate in hexane. The product fractions were concentrated by evaporation under reduced pressure to obtain 3.4 g (37 percent of theory) of the title compound as a dark low-melting solid.
Reaction SMILES: [CH2:1]([N:8]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([C:28](O)=[O:29])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl>[CH2:1]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:28]([CH:25]2[CH2:26][CH2:27][N:22]([C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:21])[CH2:23][CH2:24]2)=[O:29])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(CN2CCCNCC2)cc1
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)CC1
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: ClCCCl
Product: CC(C)(C)OC(=O)N1CCC(C(=O)N2CCCN(Cc3ccccc3)CC2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 89 %

Procedure:
1-Benzyl-[1,4]-diazepane (3.78 g) and 1-tert-butoxycarbonyl-piperidine-4-carboxylic acid (5.0 g) were dissolved in DCM (150 ml) and TEA (3.6 ml) was added followed by HOBT (1.34 g) and finally EDC (4.90 g). The reaction was stirred at rt overnight. The reaction mixture was then evaporated to a minimum, re-dissolved in DCM (50 ml) and washed with saturated sodium hydrogen carbonate solution (3×50 ml) and brine (50 ml). The organic layer was dried (MgSO4) and evaporated to a crude which was purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM]. Fractions containing pure desired product were combined and evaporated to give the subtitled compound as a pale brown solid (7.1 g).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:13](=[O:14])[C:12]2[CH:15]=[C:16]([S:18](Cl)(=[O:20])=[O:19])[S:17][C:11]=2[N:10]=[C:9]1[CH3:22].ClCCl.[C:26]([NH:29][CH2:30][CH2:31][CH2:32][CH2:33][NH2:34])(=[O:28])[CH3:27]>C(N(CC)CC)C>[C:26]([NH:29][CH2:30][CH2:31][CH2:32][CH2:33][NH:34][S:18]([C:16]1[S:17][C:11]2[N:10]=[C:9]([CH3:22])[N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[C:13](=[O:14])[C:12]=2[CH:15]=1)(=[O:20])=[O:19])(=[O:28])[CH3:27]
Reactant: Cc1nc2sc(S(=O)(=O)Cl)cc2c(=O)n1-c1ccccc1Cl
Reactant: CC(=O)NCCCCN
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)NCCCCNS(=O)(=O)c1cc2c(=O)n(-c3ccccc3Cl)c(C)nc2s1
Temperature: 25 °C
Reaction time: 3 h
Yield: 44.4 %

Procedure:
To 8.0 g of 3,4-dihydro-3-(2-chlorophenyl)-6-chlorosulfonyl-2-methyl-4-oxothieno[2,3-d]pyrimidine were added 150 ml of dichloromethane, 3.3 g of 4-acetylaminobutylamine and 5.9 ml of triethylamine, and the mixture was stirred at room temperature for 3 hours. After the reaction mixture was washed with water, the concentrated residue was purified by means of silica gel chromatography to obtain 5.71 g of oily substance, which was crystallized from ethyl acetate-hexane to afford 4.44 g of the title compound, m.p. 203°-206° C. (decomposition).