Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[NH2:2][C@@H:3]1[C:9](=[O:10])[N:8]([CH2:11][C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C:7]2[CH:22]=[CH:23][CH:24]=[CH:25][C:6]=2[O:5][CH2:4]1.C(N(CC)CC)C.Br[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>C(O)C>[CH2:38]([O:37][C:35]([CH2:34][NH:2][C@@H:3]1[C:9](=[O:10])[N:8]([CH2:11][C:12]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:13])[C:7]2[CH:22]=[CH:23][CH:24]=[CH:25][C:6]=2[O:5][CH2:4]1)=[O:36])[CH3:39]
Reactant: CCOC(=O)CBr
Reactant: N[C@H]1COc2ccccc2N(CC(=O)OCc2ccccc2)C1=O
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCOC(=O)CN[C@H]1COc2ccccc2N(CC(=O)OCc2ccccc2)C1=O
Reaction time: 96 h
Yield: 49.3 %

Procedure:
In 10 ml of ethanol is dissolved 0.5 g of benzyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate hydrochloride obtained in Example 5, and triethylamine (0.49 g) and ethyl bromoacetate (0.46 g) are added to the solution. After the solution is stirred for 4 days, the solution is dried under reduced pressure. The residue is purified by silica gel column chromatography (hexane:ethyl acetate=4:3) to give 0.28 g of benzyl 3(S)-ethoxycarbonylmethylamino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate as a pale yellow oil.
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH2:12][CH2:11][C:10]2([C:14]3[NH:22][C:21]4[C:20](=[O:23])[N:19]([CH2:24][CH2:25][CH3:26])[C:18](=[O:27])[N:17]([CH2:28][CH2:29][CH3:30])[C:16]=4[N:15]=3)[O:13][CH:6]1[CH2:7][CH2:8][CH2:9]2)=[O:4].[Li+].[OH-]>CO>[O:27]=[C:18]1[N:17]([CH2:28][CH2:29][CH3:30])[C:16]2[N:15]=[C:14]([C:10]34[O:13][CH:6]([CH2:7][CH2:8][CH2:9]3)[CH:5]([C:3]([OH:4])=[O:2])[CH2:12][CH2:11]4)[NH:22][C:21]=2[C:20](=[O:23])[N:19]1[CH2:24][CH2:25][CH3:26]
Reactant: CCCn1c(=O)c2[nH]c(C34CCCC(O3)C(C(=O)OC)CC4)nc2n(CCC)c1=O
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: CCCn1c(=O)c2[nH]c(C34CCCC(O3)C(C(=O)O)CC4)nc2n(CCC)c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
5-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-9-oxa-bicyclo[3.3.1]nonane-2-carboxylic acid methyl ester (50 mg, from step 2) was taken in MeOH (5 ml). LiOH (15 mg) was added and stirred at rt overnight. Next day MeOH was removed under reduced pressure, diluted with water and extracted with ethyl acetate. Aqueous layer was acidified with 1N HCl, extracted with ethyl acetate (3×25 ml). Combined organic layer was washed with brine, and dried over Na2SO4. Concentration of the solvent gave a white solid, which was purified by crystallizing from ether. Mass (ES+ 405)
Reaction SMILES: F[C@@H]1[C@@H](NC2C3C(=CC=C(C)C=3)N=C(N3CC4C=CC=CC=4S(=O)CC3)N=2)CN(C(OCC2C=CC=CC=2)=O)C1.[CH3:41][C:42]1[CH:43]=[C:44]2[C:49](=[CH:50][CH:51]=1)[N:48]=[C:47]([N:52]1[CH2:58][C:57]3[CH:59]=[CH:60][CH:61]=[CH:62][C:56]=3[S:55](=[O:63])[CH2:54][CH2:53]1)[NH:46][C:45]2=O.[NH:65]1[CH2:69][CH2:68][CH:67]([NH:70][C:71](=[O:77])[O:72][C:73]([CH3:76])([CH3:75])[CH3:74])[CH2:66]1>>[CH3:41][C:42]1[CH:43]=[C:44]2[C:49](=[CH:50][CH:51]=1)[N:48]=[C:47]([N:52]1[CH2:58][C:57]3[CH:59]=[CH:60][CH:61]=[CH:62][C:56]=3[S:55](=[O:63])[CH2:54][CH2:53]1)[N:46]=[C:45]2[N:65]1[CH2:69][CH2:68][CH:67]([NH:70][C:71](=[O:77])[O:72][C:73]([CH3:75])([CH3:74])[CH3:76])[CH2:66]1
Reactant: CC(C)(C)OC(=O)NC1CCNC1
Reactant: Cc1ccc2nc(N3CCS(=O)c4ccccc4C3)[nH]c(=O)c2c1
Agent: Cc1ccc2nc(N3CCS(=O)c4ccccc4C3)nc(N[C@H]3CN(C(=O)OCc4ccccc4)C[C@@H]3F)c2c1
Product: Cc1ccc2nc(N3CCS(=O)c4ccccc4C3)nc(N3CCC(NC(=O)OC(C)(C)C)C3)c2c1

Procedure:
The title compound was prepared in analogy to benzyl (3S,4S)-3-fluoro-4-{[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]amino}pyrrolidine-1-carboxylate in Example 92 by using 6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4(3H)-one and tert-butyl (pyrrolidin-3-yl)carbamate.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]([O:9]CC)=O)[C:4](=[O:12])[N:3]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+].Cl.[CH3:22][O:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([O:34][C:35]3[CH:36]=[CH:37][C:38]([NH2:41])=[N:39][CH:40]=3)=[CH:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CO.O.CN(C=O)C.CCOC(C)=O.ClCCl>[CH3:22][O:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([O:34][C:35]3[CH:36]=[CH:37][C:38]([NH:41][C:7]([C:5]4[C:4](=[O:12])[N:3]([C:13]5[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=5)[N:2]([CH3:1])[CH:6]=4)=[O:9])=[N:39][CH:40]=3)=[CH:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1
Reactant: CCOC(=O)c1cn(C)n(-c2ccccc2)c1=O
Reactant: COc1ccc2c(Oc3ccc(N)nc3)ccnc2c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1ccc2c(Oc3ccc(NC(=O)c4cn(C)n(-c5ccccc5)c4=O)nc3)ccnc2c1
Temperature: 60 °C
Reaction time: 2 h
Yield: 20.3 %

Procedure:
A solution of ethyl 1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylate (260 mg, 1056 μmol) in MeOH was treated with NaOH (1000 μl, 5000 μmol) in H2O (3 mL). The mixture was heated to 60° C. for 30 min and then cooled to room temperature. Then, the mixture was neutralized with aq. HCl (5 N, 1.1 mL) and concentrated to dryness. The residue was further dried with (azeotrope distillation with toluene, 3×5 mL). The resulting carboxylic acid was mixed with 5-(7-methoxyquinolin-4-yloxy)pyridin-2-amine (282 mg, 1054 μmol), Et3N (500 μl, 3587 μmol), and HATU (401 mg, 1054 μmol) in DMF (4 mL)-dichloromethane (5 mL) and was stirred at 60° C. for 2 h. Upon cooling to room temperature, the mixture was diluted with EtOAc containing 10% MeOH (30 mL) and washed with H2O. The organic layer was dried over Na2SO4, concentrated, and eluded on silica (1-10% 2N NH3-MeOH in CHCl3). The product was further purified on preparative HPLC to afford a white powder (100 mg, 20%).
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7]([N:12]=[N:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N+:20]([O-])=O)[CH:6]=1>[OH-].[Na+].[Zn]>[N:13]1[N:12]([C:7]2[CH:6]=[C:5]([CH2:4][CH2:3][CH2:2][OH:1])[CH:10]=[CH:9][C:8]=2[OH:11])[N:20]=[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=12
Reactant: O=[N+]([O-])c1ccccc1N=Nc1cc(CCCO)ccc1O
Agent: [Na+]
Agent: [OH-]
Agent: [Zn]
Product: OCCCc1ccc(O)c(-n2nc3ccccc3n2)c1
Yield: 80.9 %

Procedure:
5.60 g (18 mmols) of crude 4-(3-hydroxypropyl)-2-[(2-nitrophenyl)azo]phenol synthesized in Example 5 was dissolved in 18 ml of aqueous solution of 2N sodium hydroxide. Subsequently, 9 ml of previously prepared aqueous solution of 25% sodium hydroxide and 5.4 g (83 mmols) of zinc powder were simultaneously added over a period of about 3 hours. The subsequent treatment was carried out in the same manner as in Example 6, giving 3.92 g of 2-(2H-benzotriazole-2-yl)-4-(3-hydroxypropyl)phenol as pale yellow crystals (yield 72%, purity 89%).
Reaction SMILES: [O:1]1C=CC=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH3:17])([CH3:16])[C:13]([NH2:15])=[O:14])=[CH:8][CH:7]=1.CC#N.C(Cl)(Cl)(Cl)Cl.[OH2:26]>C(OCC)(=O)C>[C:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH3:17])([CH3:16])[C:13]([NH2:15])=[O:14])=[CH:8][CH:7]=1)([OH:1])=[O:26]
Reactant: CC(C)(C(N)=O)c1ccc(-c2ccco2)cc1
Reactant: O
Solvent: CC#N
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCOC(C)=O
Product: CC(C)(C(N)=O)c1ccc(C(=O)O)cc1
Reaction time: 1.5 h

Procedure:
To a solution of 2-(4-(furan-2-yl)-phenyl)-2-methyl-propionamide (reference example 26) (124 mg, 0.5 mmol) in CH3CN/CCl4/H2O (7 mL, 2/2/3) is added NaIO4 (420 mg, 2 mmol) followed by RuCl3 (H2O)(3 mg). The resulting mixture is stirred vigorously for 1.5 h, then diluted with ethyl acetate, washed with water and brine, dried over MgSO4 and concentrated to give 100 mg of the title compound as an orange solid. 1H NMR (CD3OD) d 1.58 (s, 6H), 7.50 (d, J=8 Hz, 2H), 7.98 (d, J=8 Hz, 2H). MS (EI) m/z 208 (M+H).
Reaction SMILES: Br[C:2]1[C:10]2[S:9][CH:8]=[N:7][C:6]=2[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1.[CH3:14][Sn](C)(C)C>CCOC(C)=O>[CH3:14][C:2]1[C:10]2[S:9][CH:8]=[N:7][C:6]=2[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1
Reactant: O=[N+]([O-])c1cc(Br)c2scnc2c1
Reactant: C[Sn](C)(C)C
Solvent: CCOC(C)=O
Product: Cc1cc([N+](=O)[O-])cc2ncsc12
Yield: 67 %

Procedure:
A solution of 7-bromo-5-nitrobenzothiazole (0.15 g, 0.58 mmol), tetramethyltin (0.20 mL, 0.1.5 mmol) and catalytic amount of Cl2Pd(PPh3)2 in a sealed tube was stirred for 12 h at 90° C. The reaction mixture was diluted with EtOAc and washed with brine several times. Organic solution was dried over Na2SO4 and concentrated in vacuo, yielding an oil which was subjected to column chromatography (EtOAc, neat) to provide 65 mg (0.32 mmol, 67%) of the desired product.
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([N:16]2[CH2:20][CH2:19][C:18]([F:22])([F:21])[CH2:17]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][CH3:15])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2].C(C1N=C(N2CCC(F)(F)C2)C2N=NNC=2N=1)(C)(C)C.BrCC1[CH:50]=[CH:49][C:48]([F:51])=[CH:47][C:46]=1[Cl:52]>>[C:1]([C:5]1[N:6]=[C:7]([N:16]2[CH2:20][CH2:19][C:18]([F:21])([F:22])[CH2:17]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:50]=[CH:49][C:48]([F:51])=[CH:47][C:46]=3[Cl:52])[C:9]=2[N:10]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CCn1nnc2c(N3CCC(F)(F)C3)nc(C(C)(C)C)nc21
Reactant: Fc1ccc(CBr)c(Cl)c1
Agent: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nn[nH]c2n1
Product: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nnn(Cc3ccc(F)cc3Cl)c2n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoro-pyrrolidin-1-yl)-3-ethyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 61), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 1-(bromomethyl)-2-chloro-4-fluorobenzene and isolated as colorless gum (5.8 mg, 33%). MS (m/e): 425.4 (MH+).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21](S(C)(=O)=O)[N:20]=2)=[CH:10][CH:9]=1)=[O:6].[CH3:38][N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1>>[F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([N:42]3[CH2:43][CH2:44][N:39]([CH3:38])[CH2:40][CH2:41]3)[N:20]=2)=[CH:10][CH:9]=1)=[O:6]
Reactant: CS(=O)(=O)c1nccc(Oc2ccc(NC(=O)c3cc(F)cc(N4CCOCC4)c3)c3ccccc23)n1
Reactant: CN1CCNCC1
Product: CN1CCN(c2nccc(Oc3ccc(NC(=O)c4cc(F)cc(N5CCOCC5)c4)c4ccccc34)n2)CC1

Procedure:
Compound is prepared from 3-fluoro-N-(4-{[2-(methylsulfonyl)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide and N-methylpiperazine according to conditions described in general procedure C. Mp: 195-197° C.; 1H NMR (400 MHz, CDCl3) δ 2.35 (s, 3 H), 2.39 (t, J=4.4 Hz, 4 H), 3.25 (t, J=4.8 Hz, 4 H), 3.69 (s, 4 H), 3.87 (t, J=4.4 Hz, 4 H), 6.01 (d, J=5.6 Hz, 1 H), 6.78 (d, J=11.6 Hz, 1 H), 7.07 (d, J=8.0 Hz, 1 H), 7.30-7.32 (m, 2 H), 7.49-7.59 (m, 2 H), 7.89-8.00 (m, 3 H), 8.15-8.18 (m, 2 H).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([S:10]([N:13]([CH2:48][CH:49]([CH3:51])[CH3:50])[CH2:14][C@@H:15]([OH:47])[C@@H:16]([NH:35][C:36](=[O:46])[O:37][C@@H:38]3[C@H:45]4[C@H:41]([O:42][CH2:43][CH2:44]4)[O:40][CH2:39]3)[CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][NH:27]C(OC(C)(C)C)=O)=[CH:20][CH:19]=3)(=[O:12])=[O:11])=[CH:9][C:4]=2[O:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:27][CH2:26][CH2:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][C@H:16]([NH:35][C:36](=[O:46])[O:37][C@@H:38]2[C@H:45]3[C@H:41]([O:42][CH2:43][CH2:44]3)[O:40][CH2:39]2)[C@H:15]([OH:47])[CH2:14][N:13]([S:10]([C:8]2[CH:7]=[CH:6][C:5]3[O:1][CH2:2][O:3][C:4]=3[CH:9]=2)(=[O:11])=[O:12])[CH2:48][CH:49]([CH3:51])[CH3:50])=[CH:19][CH:20]=1
Reactant: CC(C)CN(C[C@@H](O)[C@H](Cc1ccc(OCCNC(=O)OC(C)(C)C)cc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21)S(=O)(=O)c1ccc2c(c1)OCO2
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)CN(C[C@@H](O)[C@H](Cc1ccc(OCCN)cc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21)S(=O)(=O)c1ccc2c(c1)OCO2
Temperature: 25 °C
Yield: 70.7 %

Procedure:
A solution of 0.65 g (0.89 mmol) of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-1-(4-{2-[(tert-butoxycarbonyl)amino]ethoxy}benzyl)-2-hydroxypropylcarbamate in 10 mL of anhydrous CH2Cl2 was treated with 15 mL of TFA and the resulting solution was stirred at RT. After 2 hours the solution was evaporated at reduced pressure and the residue redissolved in CH2Cl2. The solution was washed with 0.5 M aqueous NaOH (1×), water (2×), dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 95:5 CH2Cl2/2M NH3 in MeOH) to afford 0.40 g (70%) of the desired compound as a white foam. 1H NMR (CDCl3): 7.39 (dd, 1H), 7.12 (s, 1H), 7.08 (d, 2H), 6.84 (d, 1H), 6.77 (d, 2H), 6.03 (s, 2H), 5.61 (d, 1H), 4.95 (m, 2H), 4.00-3.60 (m, 8H), 3.16-2.62 (m, 10H), 2.20-1.40 (m, 5H), 0.90 (d, 3H), 0.82 (d, 3H). MS(ESI): 636(M+H).
Reaction SMILES: C(B1O[C:9]([CH3:11])([CH3:10])[C:6]([CH3:8])([CH3:7])O1)(C)=C.C([O:15][C:16]([C:18]1[CH:19]=[N:20][N:21]([C:24]2[CH:29]=CC(Br)=C[N:25]=2)[C:22]=1[CH3:23])=[O:17])C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.O1CCCC1>[CH:9]([C:6]1[CH:7]=[CH:29][C:24]([N:21]2[C:22]([CH3:23])=[C:18]([C:16]([OH:17])=[O:15])[CH:19]=[N:20]2)=[N:25][CH:8]=1)([CH3:10])[CH3:11]
Reactant: CCOC(=O)c1cnn(-c2ccc(Br)cn2)c1C
Reactant: C=C(C)B1OC(C)(C)C(C)(C)O1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: COc1cccc(OC)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: C1CCOC1
Solvent: O
Product: Cc1c(C(=O)O)cnn1-c1ccc(C(C)C)cn1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
Isopropenylboronic acid pinacol ester (5.2 ml) was added to 1-(5-bromopyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (6.2 g) described in Reference Example 24(2), palladium (II) acetate (448 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos) (820 mg), tripotassium phosphate (0.6 g) and tetrahydrofuran (20 ml), and the mixture was stirred at 100° C. for 8 hours. Water was added and the reaction mixture was extracted with ethyl acetate and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated in vacuo. To the resultant yellow oil was added 1,4-Dioxane (25 ml) and 10% palladium-carbon (containing ca. 50% of water; 500 mg), and the mixture was stirred under hydrogen atmosphere at room temperature for 5 hours. The reaction solution was filtered through Celite, the filtrate was concentrated in vacuo and the residue was purified with silica gel column chromatography (n-hexane/ethyl acetate). 4N Aqueous solution of sodium hydroxide (5 ml), water (5 ml) and ethanol (10 ml) were added to the resulting oily residue and stirred at 80° C. for 4 hours. The reaction solution was concentrated in vacuo, 1N hydrochloric acid aqueous solution was added to the resulting residue at 0° C., and the precipitated solid was washed with water to give the titled compound (1.56 g) as a pale red solid.
Reaction SMILES: [CH3:1][CH:2]([N:10]1[CH:14]=[C:13]([C:15]2[C:16]3[CH:23]=[CH:22][N:21]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:17]=3[N:18]=[CH:19][N:20]=2)[CH:12]=[N:11]1)[CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.CCN(C(C)C)C(C)C.[CH3:41][N:42]1[CH:46]=[CH:45][C:44]([S:47](Cl)(=[O:49])=[O:48])=[N:43]1>C(Cl)Cl>[CH3:1][CH:2]([N:10]1[CH:14]=[C:13]([C:15]2[C:16]3[CH:23]=[CH:22][N:21]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:29])[CH3:31])[C:17]=3[N:18]=[CH:19][N:20]=2)[CH:12]=[N:11]1)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([S:47]([C:44]2[CH:45]=[CH:46][N:42]([CH3:41])[N:43]=2)(=[O:49])=[O:48])[CH2:6][CH2:5]1
Reactant: CC(CN1CCNCC1)n1cc(-c2ncnc3c2ccn3COCC[Si](C)(C)C)cn1
Reactant: Cn1ccc(S(=O)(=O)Cl)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(CN1CCN(S(=O)(=O)c2ccn(C)n2)CC1)n1cc(-c2ncnc3c2ccn3COCC[Si](C)(C)C)cn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of 4-[1-(1-methyl-2-piperazin-1-ylethyl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (0.21 g, 0.48 mmol) and DIPEA (0.26 mL, 0.0015 mol) in DCM (5 mL) was added 1-methyl-1H-pyrazole-3-sulfonyl chloride (0.14 g, 0.78 mmol) in portions at 0° C. The reaction mixture was stirred at RT overnight, quenched with water, and extracted with DCM. The organic layers were dried over MgSO4, concentrated and purified on silica gel (eluting with 0-5% MeOH in DCM) to give the desired product. LCMS calculated for C26H40N9O3SSi(M+H)+: m/z=586.3; Found: 586.4.
Reaction SMILES: OCCN1CCN(CC(NC2C(SC)=NC(C)=CC=2SC)=O)CC1.O[CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]([NH:37][C:38]2[C:39]([O:51][CH2:52][C:53]([F:56])([F:55])[F:54])=[N:40][C:41]([CH3:50])=[CH:42][C:43]=2[O:44][CH2:45][C:46]([F:49])([F:48])[F:47])=[O:36])[CH2:30][CH2:29]1.SC1NC2C=CC=CC=2N=1.[F:67][C:68]1[CH:77]=[CH:76][C:71]2[N:72]=[C:73]([SH:75])[NH:74][C:70]=2[CH:69]=1>>[F:67][C:68]1[CH:77]=[CH:76][C:71]2[N:72]=[C:73]([S:75][CH2:26][CH2:27][N:28]3[CH2:29][CH2:30][N:31]([CH2:34][C:35]([NH:37][C:38]4[C:39]([O:51][CH2:52][C:53]([F:56])([F:55])[F:54])=[N:40][C:41]([CH3:50])=[CH:42][C:43]=4[O:44][CH2:45][C:46]([F:48])([F:49])[F:47])=[O:36])[CH2:32][CH2:33]3)[NH:74][C:70]=2[CH:69]=1
Reactant: Fc1ccc2nc(S)[nH]c2c1
Reactant: Cc1cc(OCC(F)(F)F)c(NC(=O)CN2CCN(CCO)CC2)c(OCC(F)(F)F)n1
Agent: CSc1cc(C)nc(SC)c1NC(=O)CN1CCN(CCO)CC1
Agent: Sc1nc2ccccc2[nH]1
Product: Cc1cc(OCC(F)(F)F)c(NC(=O)CN2CCN(CCSc3nc4ccc(F)cc4[nH]3)CC2)c(OCC(F)(F)F)n1

Procedure:
The reaction and treatments of Example 12 were repeated, except that 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide was replaced by 2-[4-(2-hydroxyethyl) piperazin-1-yl]-N-[2, 4-bis(2,2,2-trifluoroethoxy)-6-methylpyridin-3-yl]acetamide, and 2-mercaptobenzimidazole was replaced by 5-fluoro-2-mercaptobenzimidazole, to thereby yield the title compound as a pale brown foamed substance.
Reaction SMILES: C1CO[C:8]23OCCO[C:3]2([C@:4]2([CH2:27][CH2:26][C@H:25]4[C@@H:15]([CH2:16]/[C:17](=[N:28]\[OH:29])/[CH:18]5[C@:23]4([CH3:24])[CH2:22][CH2:21][CH2:20][CH2:19]5)[C@@H:6]2[CH2:7]3)[CH3:5])[O:2]1.C([C@@H]1C2[C@](C)(CCC(=[O:50])C2)[C@@H]2[C@H]([C@H]3[C@@](CC2)(C)C(=O)CC3)C1)#N>>[OH:29]/[N:28]=[C:17]1\[CH2:16][C@@H:15]2[C@@H:25]([C@:23]3([CH3:24])[CH:18]\1[CH2:19][C:20](=[O:50])[CH2:21][CH2:22]3)[CH2:26][CH2:27][C@@:4]1([CH3:5])[C@H:6]2[CH2:7][CH2:8][C:3]1=[O:2]
Reactant: C[C@]12CCC(=O)CC1[C@@H](C#N)C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Reactant: C[C@]12CCCCC1/C(=N/O)C[C@@H]1[C@@H]2CC[C@@]2(C)[C@H]1CC13OCCOC12OCCO3
Product: C[C@]12CCC(=O)CC1/C(=N/O)C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Yield: 70 %

Procedure:
The title compound II-at was prepared in 70% yield from 3,3:17,17-bis(ethylendioxy)-6(E)-hydroxyiminoandrostane by the procedure described above for the preparation of 6α-cyanoandrostane-3,17-dione (II-ac, Prepn. 3). The combined organic extracts were washed with H2O, dried over Na2SO4 and evaporated to dryness. The residue was purified by flash chromatography (SiO2, n-hexane/acetone 70/30). 1H-NMR (300 MHz, DMSO-d6, ppm from TMS): δ 10.61 (s, 1H), 3.29 (dd, 1H), 2.61-1.03 (m, 19H), 0.88 (s, 3H), 0.79 (s, 3H).
Reaction SMILES: C[N:2](C)[CH:3]=[CH:4][C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)[N:8]=1)=O.Cl.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[NH:34]N.CCN(CC)CC>C(O)C>[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[N:34]1[C:5]([C:7]2[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)[N:8]=2)=[CH:4][CH:3]=[N:2]1
Reactant: CN(C)C=CC(=O)c1nn(-c2cccc(C(F)(F)F)c2)ccc1=O
Reactant: COc1ccccc1NN
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: COc1ccccc1-n1nccc1-c1nn(-c2cccc(C(F)(F)F)c2)ccc1=O
Temperature: 100 °C
Reaction time: 3 h
Yield: 18.9 %

Procedure:
To a solution of 3-[3-(dimethylamino)prop-2-enoyl]-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (337 mg, 1.0 mmol) in ethanol (100 mL) were added 2-methoxyphenylhydrazine hydrochloride (262 mg, 1.5 mmol) and Et3N (0.28 mL, 2.0 mmol). The mixture was stirred at 100° C. for 3 h and the solvent was removed under reduced pressure. Preparative HPLC chromatography provided 3-[1-(2-methoxyphenyl)-1H-pyrazol-5-yl]-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one as a pale yellow solid (78 mg, 19%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][OH:7].C(N[C:17]1[CH:53]=[CH:52][N:20]([C@@H:21]2[O:51][C@H:25]([CH2:26][O:27][C:28]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)([C:37]3[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=3)[C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[C@@H:23]([OH:24])[CH2:22]2)[C:19](=[O:54])[N:18]=1)(=O)C1C=CC=CC=1.N12CCCNC1=NCCC2>CC(O)C>[OH:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:17]1[CH:53]=[CH:52][N:20]([C@@H:21]2[O:51][C@H:25]([CH2:26][O:27][C:28]([C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=3)([C:37]3[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=3)[C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[C@@H:23]([OH:24])[CH2:22]2)[C:19](=[O:54])[N:18]=1
Reactant: NCCCCCO
Reactant: COc1ccc(C(OC[C@H]2O[C@@H](n3ccc(NC(=O)c4ccccc4)nc3=O)C[C@@H]2O)(c2ccccc2)c2ccc(OC)cc2)cc1
Agent: C1CN=C2NCCCN2C1
Solvent: CC(C)O
Product: COc1ccc(C(OC[C@H]2O[C@@H](n3ccc(NCCCCCO)nc3=O)C[C@@H]2O)(c2ccccc2)c2ccc(OC)cc2)cc1

Procedure:
A solution of 5-aminopentanol (10.0 g, 96.9 mmol) in 2-propanol (10 mL) was added to N4-benzoyl-2′-deoxy-5′-O-(4,4′-dimethoxytrityl)cytidine (2.61 g, 4.12 mmol) and stirred until the mixture was clear. 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD, 2.40 g, 17.2 mmol) was added and the reaction mixture was stirred at ambient temperature for 48 hours. The reaction mixture was evaporated to an oil under high vacuum via oil pump, dissolved in CHCl3 (100 mL), extracted with 0.1 molar aqueous NaOH (2×50 mL) and water (4×50 mL). The organic phase was dried with anhydrous Na2SO4, evaporated, and dissolved in CH2Cl2. The organic phase was evaporated to an oil and purified by silica gel column chromatography using 2:4:94 Et3N:MeOH:CH2Cl2 and 2.5:5:92.5 Et3N:MeOH:CH2Cl2; v/v/v as the eluent. The purification was repeated until a reasonably pure product was obtained. The removal of side product 2′-deoxy-5′-O-(4,4′-dimethoxytrityl)-cytidine was responsible for the necessary of additional purification. After purification 0.53 g (18%) of the title compound was isolated.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][C:5]([OH:7])=[O:6].BrCCCCCC(O[C:17]([CH3:20])([CH3:19])[CH3:18])=O>C=C(C)C>[Br:1][CH2:2][CH2:3][CH2:4][C:5]([O:7][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:6]
Reactant: O=C(O)CCCBr
Reactant: CC(C)(C)OC(=O)CCCCCBr
Agent: C=C(C)C
Product: CC(C)(C)OC(=O)CCCBr
Yield: 54 %

Procedure:
4-Bromobutanoic acid (8 g, 47.9 mmol) and iso-butene (60 ml) were reacted by the same procedure as described in Example 1 for the preparation of tert-butyl 6-bromohexanoate to give the title material (5.7 g, 54%) as a colorless liquid (b.p. 62-64° C./10 mmHg).