Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+].[CH3:3][C@@:4]12[C:20](=[O:21])[CH2:19][CH2:18][C@H:17]1[C@H:16]1[C@@H:7]([C:8]3[CH:9]=[CH:10][C:11]([OH:22])=[CH:12][C:13]=3[CH2:14][CH2:15]1)[CH2:6][CH2:5]2.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH:29]=O.CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O>C(O)C>[OH:22][C:11]1[CH:10]=[CH:9][C:8]2[CH:7]3[CH:16]([CH2:15][CH2:14][C:13]=2[CH:12]=1)[CH:17]1[C:4]([CH3:3])([C:20](=[O:21])[C:19](=[CH:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=2)[CH2:18]1)[CH2:5][CH2:6]3
Reactant: C[C@]12CC[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1CCC2=O
Reactant: O=Cc1ccccn1
Agent: CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC12CCC3c4ccc(O)cc4CCC3C1CC(=Cc1ccccn1)C2=O
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Sodium hydroxide (1.0 g, 25 mmol) was added to a suspension of estrone (1.35 g, 5.0 mmol) and pyridine-2-carbaldehyde (595 mg, 5.0 mmol) in ethanol (40 mL) at room temperature. The resulting dark orange solution was stirred at room temperature for 4 hours. Then glacial acetic (ca. 10 mL) acid was added with stirring. The colour changed to light yellow and a light yellow solid precipitated. The solid was filtered off and washed with water (50 mL), ethanol (20 mL), diethyl ether (50 mL) and hexane (50 mL) and dried under high vacuum. Yield: 1.638 g (91%) yellow powder.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[C:9](Cl)(Cl)=[S:10].C(N(CC)CC)C>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[N:4]=[C:9]=[S:10]
Reactant: Nc1ccccc1F
Reactant: S=C(Cl)Cl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: Fc1ccccc1N=C=S
Temperature: 25 °C
Reaction time: 16 h
Yield: 76.2 %

Procedure:
Into a solution of 2-fluoroaniline (1.0 g, 9.0 mmol) in 30 mL of toluene at room temperature, thiophosgene (1.06 mL, 13.5 mmol) and triethylamine (1.55 mL, 13.5 mmol) was added. The mixture was stirred at room temperature for 16 hours. The mixture was partitioned between ethyl acetate and water. The combined organic layer was then concentrated to give the desired product (1.05 g, 76%). 1H NMR (CDCl3) δ 7.1-7.3 (m, 4H).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][C:10]2[C:11](=[O:20])[N:12]=[C:13]([NH:16][N+]([O-])=O)[NH:14][CH:15]=2)=[CH:5][N:4]=1.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]2[CH:34]=[CH:33][C:32]([CH2:35][CH2:36]N)=[CH:31][CH:30]=2)=[CH:24][C:23]=1[C:38]([F:41])([F:40])[F:39]>C(O)C>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]2[CH:30]=[CH:31][C:32]([CH2:35][CH2:36][NH:16][C:13]3[NH:14][CH:15]=[C:10]([CH2:9][C:6]4[CH:5]=[N:4][C:3]([O:2][CH3:1])=[N:8][CH:7]=4)[C:11](=[O:20])[N:12]=3)=[CH:33][CH:34]=2)=[CH:24][C:23]=1[C:38]([F:39])([F:40])[F:41]
Reactant: COc1ncc(Cc2c[nH]c(N[N+](=O)[O-])nc2=O)cn1
Reactant: NCCc1ccc(Oc2ccc(Cl)c(C(F)(F)F)c2)cc1
Solvent: CCO
Product: COc1ncc(Cc2c[nH]c(NCCc3ccc(Oc4ccc(Cl)c(C(F)(F)F)c4)cc3)nc2=O)cn1
Temperature: 100 °C
Yield: 48.2 %

Procedure:
To the solution of 5-{[2-(methyloxy)-5-pyrimidinyl]methyl}-2-(nitroamino)-4(1H)-pyrimidinone (100 mg, 0.359 mmol) in ethanol (5 mL) was added neat 2-(4-{[4-chloro-3-(trifluoromethyl)-phenyl]oxy}phenyl)ethanamine (189 mg, 0.599 mmol). It was heated with a microwave reactor at 100° C. overnight. Purification via MDAP then afforded the title compound (92 mg, 35.6% yield). LCMS: rt=3.04 min, [M+H+]=532.2
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:13])=[C:4]([O:11][CH3:12])[CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[CH2:14](Br)[C:15]#[CH:16]>>[CH2:16]([O:8][C:7](=[O:9])[C:6]1[CH:10]=[C:2]([Br:1])[C:3]([OH:13])=[C:4]([O:11][CH3:12])[CH:5]=1)[C:15]#[CH:14]
Reactant: COc1cc(C(=O)O)cc(Br)c1O
Reactant: C#CCBr
Product: C#CCOC(=O)c1cc(Br)c(O)c(OC)c1

Procedure:
By utilizing the procedure of Example 5, by reacting 5-bromovanillic acid with propargyl bromide, there is obtained 5-bromovanillic acid propargyl ester; M.P. 121-122°C.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([CH3:11])[CH:3]=1.Cl.[Cl:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[CH:20]=[C:19]([S:24]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)(=[O:26])=[O:25])[CH:18]=[CH:17]2>>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:30]2[CH2:29][CH2:28][N:27]([S:24]([C:19]3[CH:18]=[CH:17][C:16]4[C:21](=[CH:22][CH:23]=[C:14]([Cl:13])[CH:15]=4)[CH:20]=3)(=[O:26])=[O:25])[CH2:32][CH2:31]2)=[O:8])=[C:4]([CH3:11])[CH:3]=1
Reactant: O=S(=O)(c1ccc2cc(Cl)ccc2c1)N1CCNCC1
Reactant: Cc1cc(Br)ccc1C(=O)O
Agent: Cl
Product: Cc1cc(Br)ccc1C(=O)N1CCN(S(=O)(=O)c2ccc3cc(Cl)ccc3c2)CC1

Procedure:
In a similar manner to Referential Example 12 except for the use of 4-bromo-2-methylbenzoic acid and 1-[(6-chloronaphthalen-2-yl)sulfonyl]piperazine hydrochloride as the raw materials, the reaction was conducted, whereby the title compound was obtained.
Reaction SMILES: S(=O)(=O)(O)O.[NH2:6][C:7]1[N:12]=[C:11]([NH:13][C@@H:14]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:15][CH2:16][OH:17])[C:10]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][C:30]([OH:32])=[O:31])=[CH:25][C:24]=2[F:33])=[C:9]([CH3:34])[N:8]=1.[C:35]([O-])(O)=O.[Na+]>CO.O>[NH2:6][C:7]1[N:12]=[C:11]([NH:13][C@@H:14]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:15][CH2:16][OH:17])[C:10]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][C:30]([O:32][CH3:35])=[O:31])=[CH:25][C:24]=2[F:33])=[C:9]([CH3:34])[N:8]=1
Reactant: O=C([O-])O
Reactant: CCCC[C@@H](CCO)Nc1nc(N)nc(C)c1Cc1ccc(CC(=O)O)cc1F
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCCC[C@@H](CCO)Nc1nc(N)nc(C)c1Cc1ccc(CC(=O)OC)cc1F
Temperature: 70 °C

Procedure:
Concentrated sulfuric acid (0.3 mL) was added to a stirred solution of the product from step (v) (0.08 g) in MeOH (1 mL) and the mixture was heated to 70° C. for 2 h. The mixture was allowed to cool, diluted with water (2 mL) and neutralised with NaHCO3. The aqueous was extracted with EtOAc and the combined organic phase was dried and evaporated. The crude product was purified by RPHPLC to give the title compound, 0.005 g.
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[CH:8]=[N:9][N:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][C@H:23]3[CH3:27])=[CH:14][CH:13]=2)[CH:11]=1)=[O:6].[C:28]([Si:32](Cl)([CH3:34])[CH3:33])([CH3:31])([CH3:30])[CH3:29].N1C=CN=C1.CN(C)C=O>[Cl-].[Na+].O>[Si:32]([O:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[CH:8]=[N:9][N:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][C@H:23]3[CH3:27])=[CH:14][CH:13]=2)[CH:11]=1)=[O:6])([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:34])[CH3:33]
Reactant: C[C@@H]1CCCN1CCCOc1ccc(-n2cc(C(=O)NCCO)cn2)cc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: [Cl-]
Agent: [Na+]
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: C[C@@H]1CCCN1CCCOc1ccc(-n2cc(C(=O)NCCO[Si](C)(C)C(C)(C)C)cn2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.2 %

Procedure:
A mixture of N-(2-hydroxyethyl)-1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxamide prepared in Example 66 (0.500 g), tert-butylchlorodimethylsilane (0.303 g), imidazole (0.273 g) and N,N-dimethylformamide (5.0 mL) was stirred overnight at room temperature. The reaction mixture was diluted with brine and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=1:1) to give the titled compound (0.550 g) as a colorless solid.
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:18])=[CH:4][C:5]2[C:6]([CH3:17])([CH3:16])[CH2:7][CH:8]=[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:10]=2[CH:11]=1.[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[CH2:19]([O:18][C:3]1[CH:4]=[C:5]2[C:10]([C:9]([C:12]([CH3:13])([CH3:15])[CH3:14])=[CH:8][CH2:7][C:6]2([CH3:17])[CH3:16])=[CH:11][C:2]=1[Br:1])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: BrCc1ccccc1
Reactant: CC(C)(C)C1=CCC(C)(C)c2cc(O)c(Br)cc21
Product: CC(C)(C)C1=CCC(C)(C)c2cc(OCc3ccccc3)c(Br)cc21
Yield: 100 %

Procedure:
Following General Procedure O, 3-bromo-5-t-butyl-8,8-dimethyl-7,8-dihydronaphthalen-2-ol (Compound 98, 0.18 g, 0.58 mmol) was reacted with benzyl bromide to afford 0.23 g (100%) of the title compound as a yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH3:10])[C:6]=2[CH:11]=1.[Li+].CC([N-]C(C)C)C.[I:20]CCI.O>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([I:20])[N:7]([CH3:10])[C:6]=2[CH:11]=1
Reactant: Cn1cnc2ccc(Cl)cc21
Reactant: ICCI
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: Cn1c(I)nc2ccc(Cl)cc21
Temperature: -78 °C
Reaction time: 1 h

Procedure:
A flask charged with a solution of 6-chloro-1-methyl-1H-benzo[d]imidazole (2 g, 12 mmol) in THF (100 mL) was cooled to −78° C. and 1.8M LDA in THF/hexanes/ethylbenzene (9.34 mL, 16.81 mmol) was added dropwise, and the mixture was stirred at −78° C. for 1 h. A solution of 1,2-diiodoethane (3.72 g, 13.2 mmol) in THF (50 mL) was added dropwise and the mixture was stirred at −78° C. for 1 h. Water (0.3 mL) was added followed by silica gel (20 g) and the mixture was concentrated in vacuo. The residue was purified by silica chromatography eluting with EtOAc in heptane (v/v, 10 to 50%) to give 6-chloro-2-iodo-1-methyl-1H-benzo[d]imidazole. 1H NMR (400 MHz, DMSO-d6) 5 ppm 3.76 (s, 3H) 7.19 (dd, J=8.59, 2.02 Hz, 1H) 7.58 (d, J=8.59 Hz, 1H) 7.78 (d, J=2.02 Hz, 1H).
Reaction SMILES: [CH3:1][CH:2]([OH:5])[CH:3]=[CH2:4].N1C=CN=C1.[CH3:11][C:12]([Si:15](Cl)([CH3:17])[CH3:16])([CH3:14])[CH3:13]>C(Cl)Cl>[C:12]([Si:15]([CH3:17])([CH3:16])[O:5][CH:2]([CH3:1])[CH:3]=[CH2:4])([CH3:14])([CH3:13])[CH3:11]
Reactant: C=CC(C)O
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: C=CC(C)O[Si](C)(C)C(C)(C)C
Reaction time: 3 h
Yield: 84 %

Procedure:
To a solution of but-3-en-2-ol (5.0 g, 69.34 mmol) in CH2Cl2 (100 mL) at 0° C. was added imidazole (5.66 g, 1.2 eq) and TBSCl (10.45 g, 1.0 eq). The reaction mixture was stirred at 0° C. to rt for 3 h. Solid was filtered off, the filtrate was concentrated and passed through a short silica gel column by eluting with hexane to give tert-butyl-dimethyl-(1-methyl-allyloxy)-silane (10.86 g, 85%) as a colorless oil.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]3[O:16][C:15]([CH:17]4[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]4)=[N:14][C:13]=3[CH:30]=2)O1.Br[C:33]1[CH:38]=[CH:37][C:36]([N:39]2[CH:43]=[N:42][N:41]=[N:40]2)=[C:35]([F:44])[CH:34]=1>>[F:44][C:35]1[CH:34]=[C:33]([C:9]2[CH:10]=[CH:11][C:12]3[O:16][C:15]([CH:17]4[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:24])[CH2:21][CH2:22]4)=[N:14][C:13]=3[CH:30]=2)[CH:38]=[CH:37][C:36]=1[N:39]1[CH:43]=[N:42][N:41]=[N:40]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2nc3cc(B4OC(C)(C)C(C)(C)O4)ccc3o2)CC1
Reactant: Fc1cc(Br)ccc1-n1cnnn1
Product: CC(C)(C)OC(=O)N1CCC(c2nc3cc(-c4ccc(-n5cnnn5)c(F)c4)ccc3o2)CC1
Yield: 20.6 %

Procedure:
Following the General Procedure-3, the titled compound (22 mg) was prepared from Intermediate 8 (100 mg, 0.23 mmol) and 1-(4-bromo-2-fluorophenyl)-1H-tetrazole (56 mg, 0.23 mmol) as a pale-yellow solid. M.P.: 154-159° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 9.14 (d, J 2.5, 1H), 8.04 (t, J 7.8, 1H), 7.91 (d, J 3.9, 1H), 7.64-7.54 (m, 4H), 4.16 (d, J 10, 2H), 3.21-3.13 (m, 1H), 3.01 (t, J 11.9, 2H), 2.21-2.12 (m, 2H), 2.00-1.87 (m, 2H), 1.48 (s, 9H).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18]N3C(=O)C4C(=CC=CC=4)C3=O)[NH:12][C:13]=2[CH3:14])=[CH:5][CH:4]=1.[H-].[Na+].COC1C=CC(C2N=CNC=2C)=CN=1.BrCCCC[N:51]1[C:55](=[O:56])[C:54]2=[CH:57][CH:58]=[CH:59][CH:60]=[C:53]2[C:52]1=[O:61]>CN(C=O)C>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][C:57]3[CH:58]=[CH:59][CH:60]=[C:53]4[C:54]=3[C:55](=[O:56])[NH:51][C:52]4=[O:61])[NH:12][C:13]=2[CH3:14])=[CH:5][CH:4]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCCBr
Reactant: COc1ccc(-c2nc(CCCCN3C(=O)c4ccccc4C3=O)[nH]c2C)cn1
Agent: COc1ccc(-c2nc[nH]c2C)cn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(-c2nc(CCCCc3cccc4c3C(=O)NC4=O)[nH]c2C)cn1
Reaction time: 22 h
Yield: 24 %

Procedure:
2-{4-[4-(6-methoxy(3-pyridyl))-5-methylimidazolyl]butyl}-isoindole-1,3-dione. To a solution of sodium hydride, 60% dispersion (1.8 g, 44.75 mmoles) in DMF (9 ml) at 0° C. was added a solution of 2-methoxy-5-(5-methylimidazol-4-yl)pyridine (3.4 g, 17.9+mmoles) in DMF (18 ml) dropwise. A solution of N-(4-bromobutyl)phthalimide (7.6 g, 26.9 mmoles) in DMF (12 ml) was than added. The reaction was held at 0° C. for 22 hours, at which time it was dumped onto ice (400 g). The precipitate was filtered and the solid was dissolved in DCM. The organic solution was dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography using a solvent gradient of 0-1-3% MeOH in CH2Cl2 with 0.1% TEA to yield 2-{4-[4-(6-methoxy(3-pyridyl))-5-methylimidazolyl]butyl-isoindole-1,3-dione (1.6 g, 24%). MH+(391)
Reaction SMILES: CO[C:3]1[CH:11]=[CH:10][CH:9]=[C:8](OC)[C:4]=1[C:5](Cl)=[O:6].C[NH:15]CCC#CC1C=CC=CN=1.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl>[C:5]([NH2:15])(=[O:6])[C:4]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:3]=1
Reactant: COc1cccc(OC)c1C(=O)Cl
Reactant: CNCCC#Cc1ccccn1
Solvent: ClC(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Product: NC(=O)c1ccccc1
Temperature: 0 °C
Reaction time: 14 h
Yield: 11.9 %

Procedure:
2,6-Dimethoxy-benzoyl chloride (81 mg, 0.41 mmol) was added to a solution, of methyl-(4-pyridin-2-yl-but-3-ynyl)-amine (50 mg, 0.31 mmol) and DIEA (69 μL, 0.41 mmol) in chloroform (2 mL) at 0° C. The reaction mixture was stirred at 0° C. for 10 min, at room temperature for 14 hours, quenched by the addition of water and extracted twice with chloroform. The organic phase was washed with saturated solution of NaHCO3, brine, dried over MgSO4, filtered and evaporated. The crude residue was purified by flash chromatography (DCM/MeOH 95:5) to yield 2,6-dimethoxy-N-methyl-N-(pyridin-2-yl)but-3-ynyl)benzamide (12 mg, 37 μmol, 12%).
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[O:13][CH:14]=[C:15]([CH2:17][OH:18])[N:16]=2)=[CH:6][CH:5]=1.CC(C)([O-])C.[Na+].Cl[C:28]1[N:29]=[N:30][C:31]([CH2:34][CH2:35][CH2:36][CH2:37][N:38]2[CH:42]=[CH:41][N:40]=[N:39]2)=[CH:32][CH:33]=1.C(OCC)(=O)C>O1CCCC1>[N:38]1([CH2:37][CH2:36][CH2:35][CH2:34][C:31]2[N:30]=[N:29][C:28]([O:18][CH2:17][C:15]3[N:16]=[C:12]([CH:11]=[CH:10][C:7]4[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:19])[F:20])=[CH:5][CH:6]=4)[O:13][CH:14]=3)=[CH:33][CH:32]=2)[CH:42]=[CH:41][N:40]=[N:39]1
Reactant: Clc1ccc(CCCCn2ccnn2)nn1
Reactant: OCc1coc(C=Cc2ccc(OC(F)(F)F)cc2)n1
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: FC(F)(F)Oc1ccc(C=Cc2nc(COc3ccc(CCCCn4ccnn4)nn3)co2)cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
{2-[2-(4-Trifluoromethoxy-phenyl)-vinyl]-oxazol-4-yl}-methanol (0.050 g, 0.17 mmol) is dissolved in anhydrous tetrahydrofuran (THF) (2 ml) followed by addition of sodium tert-butoxide (NaOtBu) (0.019 g, 0.19 mmol). After stirring for 15 min at r.t. 3-chloro-6-(4-[1,2,3]triazol-1-yl-butyl)-pyridazine (0.035 g, 0.15 mmol) is added slowly and stirred for further 4 h at 60° C. Ethyl acetate (20 ml) is added, the mixture is washed with saturated ammonium chloride (NH4Cl), dried over Na2SO4 and concentrated in vacuo. After flash column chromatography (ethyl acetate/methanol 97:3) 3-(4-[1,2,3]triazol-1-yl-butyl)-6-{2-[2-(4-trifluoromethoxy-phenyl)-vinyl]-oxazol-4-ylmethoxy}-pyridazine is isolated as a colorless solid. Yield 0.049 g (69%).
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[CH2:15][CH2:14][NH:13][CH2:12][C:11]=2[C:10]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:31][CH2:32][CH2:33][OH:34]>CN(C=O)C.O>[CH2:1]([N:8]1[C:16]2[CH2:15][CH2:14][N:13]([CH2:31][CH2:32][CH2:33][OH:34])[CH2:12][C:11]=2[C:10]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OCCCBr
Reactant: Clc1ccc(-c2cn(Cc3ccccc3)c3c2CNCC3)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: OCCCN1CCc2c(c(-c3ccc(Cl)cc3)cn2Cc2ccccc2)C1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 1-benzyl-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine (Example 25; 0.51 g) in DMF (14 mL) was added 1.39 g of Cs2CO3 and 142 μL of 3-bromo-1-propanol. The mixture was stirred at RT for 12 h and then was diluted with water. The aqueous layer was extracted with Et2O and the combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Chromatography on SiO2 (2% 2 M NH3 in MeOH/CH2Cl2) afforded 0.15 g of the title compound. The product was dissolved in Et2O and treated with excess 1.0 M HCl in Et2O to afford 0.16 g the corresponding HCl salt. MS (ESI): exact mass calculated for C23H25ClN2O, 380.17. found, m/z 381.2 [M+H]+, 383.2 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.37-7.27 (m, 7H), 7.19-7.17 (m, 3H), 5.15 (s, 2H), 4.47 (br s, 2H), 3.93-3.25 (m, 6H), 2.94-2.93 (m, 2H), 2.01-1.96 (m, 2H).
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[S:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[Cl-].[Al+3].[Cl-].[Cl-].[C:18](Cl)(=[O:20])[CH3:19]>C(=S)=S>[C:18]([C:2]1[CH:3]=[CH:4][C:5]2[S:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[C:9]=2[CH:1]=1)(=[O:20])[CH3:19]
Reactant: CC(=O)Cl
Reactant: c1ccc2c(c1)sc1ccccc12
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: CC(=O)c1ccc2sc3ccccc3c2c1

Procedure:
Dibenzothiophene (18.4 g.) and anhydrous aluminium chloride (13.3 g.) were mechanically stirred in carbon disulphide (100 ml.) while acetyl chloride (7.85 g.) in carbon disulphide (20 ml.) was added dropwise over 0.5 hr. The temperature of the mixture rose to 30° C. After a total of 4 hr. stirring the mixture was poured on to ice and extracted with chloroform. The extract was washed with sodium bicarbonate solution, dried with magnesium sulphate, and evaporated. The residue was distilled under vacuum and a fraction, b.pt. 160°-180° C. at 0.6 mm. Hg, was extracted by boiling with ether, and the residue recrystallised twice from methanol to give colourless crystals of 2-acetyldibenzothiophene m.pt. 97°-100° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([S:14][C:15](=O)[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.C[O-].[Na+].[Br:23][CH2:24][CH2:25][CH2:26][CH2:27]CCBr>C1COCC1.CO>[Br:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:16][CH2:15][S:14][CH:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]1
Reactant: BrCCCCCCBr
Reactant: CC(=O)SC1CCN(C(=O)OC(C)(C)C)CC1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(SCCCCCCBr)CC1
Yield: 61.4 %

Procedure:
To a solution of N-t-butyloxycarbonyl-4-acetylthiopiperidine (5.5 g) in a mixture of THF (50 ml) and methanol (50 ml) was added 28% sodium methoxide methanol solution (4.76 ml) with stirring under ice-cooling and stirred at the same temperature for 30 minutes. To the solution was added 1,6-dibromohexane (17.1 g) under ice-cooling, and the mixture was successively stirred at ambient temperature for 30 minutes and then stirred at 45° C. for 2 hours. The reaction mixture was concentrated in vacuo. The resulting residue was chromatographed on silica gel (500 ml) eluting with a mixture of n-hexane and ethyl acetate (6:1 v/v). The fractions containing the desired compound were collected and evaporated under reduced pressure to give 4-(6-bromohexylthio)-N-t-butyloxycarbonylpiperidine (4.95 g).
Reaction SMILES: [CH3:1][NH:2][C:3]1[N:8]=[C:7]([S:9][CH2:10][CH2:11][O:12][CH3:13])[CH:6]=[C:5]([CH3:14])[N:4]=1.[N+:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[S:24]([N:27]=[C:28]=[O:29])(=[O:26])=[O:25])([O-:17])=[O:16]>C(Cl)Cl>[CH3:13][O:12][CH2:11][CH2:10][S:9][C:7]1[CH:6]=[C:5]([CH3:14])[N:4]=[C:3]([N:2]([CH3:1])[C:28]([NH:27][S:24]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N+:15]([O-:17])=[O:16])(=[O:26])=[O:25])=[O:29])[N:8]=1
Reactant: CNc1nc(C)cc(SCCOC)n1
Reactant: O=C=NS(=O)(=O)c1ccccc1[N+](=O)[O-]
Solvent: ClCCl
Product: COCCSc1cc(C)nc(N(C)C(=O)NS(=O)(=O)c2ccccc2[N+](=O)[O-])n1

Procedure:
By using the procedure of Equation 2 with an equivalent amount of appropriate 2-methylaminopyrimidines or 2-methylamino-1,3,5-triazines and appropriately substituted benzenesulfonylisocyanates or isothiocyanates, the compounds of Table 3 can be prepared. For example, to a dry stirred solution of 19.7 parts of 2-methylamino-4-(2-methoxyethylthio)-6-methylpyrimidine in 300 parts of methylene chloride at ambient temperature is added 22.8 parts of 2-nitrobenzenesulfonylisocyanate. That mixture is stirred and refluxed for 4 hours, and then the methylene chloride is removed under reduced pressure. The resulting solid is triturated with 1-chlorobutane to yield N-[N-[4-(2-methoxyethylthio)-6-methylpyrimidin-2-yl]-N-methylaminocarbonyl]-2-nitrobenzenesulfonamide.
Reaction SMILES: [OH:1][C@@H:2]([C@H:4]1[C:24](=[O:25])[N:6]2[C:7]([C:21]([O-:23])=[O:22])=[C:8]([S:11]/[CH:12]=[CH:13]\[C:14]3[S:18][CH:17]=[N:16][C:15]=3[CH2:19][OH:20])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].[Na+].[CH:27]([O:30][C:31]([O:33][CH2:34]I)=[O:32])([CH3:29])[CH3:28]>>[OH:1][C@@H:2]([C@H:4]1[C:24](=[O:25])[N:6]2[C:7]([C:21]([O:23][CH2:34][O:33][C:31]([O:30][CH:27]([CH3:29])[CH3:28])=[O:32])=[O:22])=[C:8]([S:11]/[CH:12]=[CH:13]\[C:14]3[S:18][CH:17]=[N:16][C:15]=3[CH2:19][OH:20])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(S/C=C\c3scnc3CO)[C@H](C)[C@H]12
Reactant: CC(C)OC(=O)OCI
Agent: [Na+]
Product: CC(C)OC(=O)OCOC(=O)C1=C(S/C=C\c2scnc2CO)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Yield: 47.3 %

Procedure:
In the same manner as in Example 81, 203 mg of the title compound was prepared from 348 mg of sodium (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-2-[[(Z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate and 252 mg of isopropyloxycarbonyloxymethyl iodide.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][N:9]2[C@H:12]2[C@H:16]([OH:17])[C@H:15]([OH:18])[C@@H:14]([CH2:19][O:20][CH3:21])[O:13]2)=[C:5]([NH:22][CH2:23][CH:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:4]=1.[CH2:37]([S:40](Cl)(=[O:42])=[O:41])[CH2:38][CH3:39].C(N(CC)CC)C>>[OH:17][C@@H:16]1[C@H:15]([OH:18])[C@@H:14]([CH2:19][O:20][CH3:21])[O:13][C@H:12]1[N:9]1[CH:8]=[N:7][C:6]2[C:10]1=[N:11][C:3]([CH2:2][NH:1][S:40]([CH2:37][CH2:38][CH3:39])(=[O:42])=[O:41])=[N:4][C:5]=2[NH:22][CH2:23][CH:24]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: CCCS(=O)(=O)Cl
Reactant: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CN)nc32)[C@H](O)[C@@H]1O
Solvent: CCN(CC)CC
Product: CCCS(=O)(=O)NCc1nc(NCC(c2ccccc2)c2ccccc2)c2ncn([C@@H]3O[C@H](COC)[C@@H](O)[C@H]3O)c2n1
Yield: 44.1 %

Procedure:
The title compound was prepared by a similar method to example 3 from (2R,3R,4S,5R)-2-{2-(aminomethyl)-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-5-(methoxymethyl)tetrahydro-3,4-furandiol (example 1) (110 mg, 0.22 mmol), 1-propanesulphonyl chloride (28 mg, 0.19 mmol) and triethylamine (0.1 ml, 0.72 mmol). The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (98:2) gradually changing to dichloromethane:methanol (95:5) to afford the title compound as a solid (50 mg). MS: 597 (MH+).