Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[O:9][C:8]([CH2:10]Br)=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>CC(C)=O.O>[C:1]([C:5]1[O:9][C:8]([CH2:10][N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)c1cc(C(C)(C)C)oc1CBr
Reactant: C1CCNCC1
Solvent: CC(C)=O
Solvent: O
Product: COC(=O)c1cc(C(C)(C)C)oc1CN1CCCCC1
Yield: 14.7 %

Procedure:
A solution of methyl 5-tert-butyl-2-(bromomethyl)furan-3-carboxylate (0.28 g, 1.0 mmol) and piperidine (99 μL, 1 mmol) in acetone (5 mL) was stirred at room temperature 3 days. The mixture was diluted with water and extracted with EtOAc. The organic extracts were washed with water, dried over Na2SO4, and concentrated under vacuum. The residue was purified by silica gel chromatography (0%-50% EtOAc-hexanes) to obtain methyl 5-tert-butyl-2-((piperidin-1-yl)methyl)furan-3-carboxylate (41 mg, 15% yield). LC/MS: m/z 280.3 (M+H)+ at 2.10 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH:8]=[C:9]([Cl:11])[Cl:10])[CH:5]=[C:4](O)[N:3]=1.P(Cl)(Cl)([Cl:15])=O>>[NH2:1][C:2]1[N:3]=[C:4]([Cl:15])[CH:5]=[C:6]([CH:8]=[C:9]([Cl:11])[Cl:10])[N:7]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Nc1nc(O)cc(C=C(Cl)Cl)n1
Product: Nc1nc(Cl)cc(C=C(Cl)Cl)n1

Procedure:
10 Parts of 2-amino-4-(2,2-dichlorovinyl)-6-hydroxypyrimidine and 66 parts of phosphorus oxychloride were heated together under reflux for 1 hour with stirring. The solution was cooled and excess phosphorus oxychloride was removed in vacuo on a rotary evaporator. The residual viscous oil was poured onto ice, with stirring. Solid sodium bicarbonate was added portionwise until the solution had pH 7-8. The precipitated solid was filtered, washed with water and dried. Recrystallisation from aqueous methanol gave 2-amino-4-chloro-6-(2,2-dichlorovinyl)pyrimidine m.p. 119°-120° C.
Reaction SMILES: [CH2:1]([C:4]1[NH:9][C:8](=O)[N:7]=[C:6]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[CH:5]=1)[CH2:2][CH3:3].P(Cl)(Cl)([Cl:23])=O>>[Cl:23][C:8]1[N:9]=[C:4]([CH2:1][CH2:2][CH3:3])[CH:5]=[C:6]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[N:7]=1
Reactant: CCCc1cc(-c2cccc(C(F)(F)F)c2)nc(=O)[nH]1
Reactant: O=P(Cl)(Cl)Cl
Product: CCCc1cc(-c2cccc(C(F)(F)F)c2)nc(Cl)n1

Procedure:
A mixture of 6-propyl-4-(3-trifluoromethylphenyl)-1H-pyrimidin-2-one (204 mg) and phosphorus oxychloride (3 mL) was stirred and heated at reflux for 72 h, then allowed to cool and poured onto a mixture of ice/ether (20 mL). The ether layer was separated, washed with saturated sodium carbonate solution (20 mL), dried over sodium sulphate, and evaporated at reduced pressure to afford 2-chloro-4-propyl-6-(3-trifluoromethylphenyl)-pyrimidine as a dark brown oil (239 mg).
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:27])=[C:4]([N:8]2[C:16]([C:18]3[CH:23]=[CH:22][C:21]([NH2:24])=[C:20]([NH2:25])[CH:19]=3)([OH:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:26])[CH:5]=[CH:6][CH:7]=1.[C:28](N1C=CN=C1)(N1C=CN=C1)=[O:29]>O1CCCC1>[Cl:1][C:2]1[C:3]([F:27])=[C:4]([N:8]2[C:9](=[O:26])[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:16]2([C:18]2[CH:23]=[CH:22][C:21]3[NH:24][C:28](=[O:29])[NH:25][C:20]=3[CH:19]=2)[OH:17])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Nc1ccc(C2(O)c3ccccc3C(=O)N2c2cccc(Cl)c2F)cc1N
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(O)(c2ccc3[nH]c(=O)[nH]c3c2)N1c1cccc(Cl)c1F
Reaction time: 2 h
Yield: 31.9 %

Procedure:
To a solution of 2-(3-chloro-2-fluorophenyl)-3-(3,4-diaminophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one (100 mg, 0.26 mmol) in tetrahydrofuran (3 mL) was added 1,1′-carbonyldiimidazole (63 mg, 0.39 mmol) at room temperature. The reaction mixture was stirred for 2 h, at which time the solvent was evaporated. The residue was purified by reverse phase HPLC to afford 5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1,3-dihydro-2H-benzimidazol-2-one (34 mg). 1H NMR (400 MHz, d6-DMSO): 10.63 (s, 1H), 10.52 (s, 1H), 7.84 (d, 1H), 7.72 (d, 1H), 7.68-7.58 (m, 2H), 7.50 (dt, 1H), 7.31-7.29 (m, 2H), 7.19 (t, 1H), 6.84-6.77 (m, 3H); MS (EI) for C21H13ClFN3O3: 408 (MH−).
Reaction SMILES: [CH3:1][N:2]1[C:15]2([CH2:17][CH2:16]2)[CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[F:18][C:19]([F:29])([F:28])[C:20]1[CH:25]=[CH:24][C:23]([CH:26]=[CH2:27])=[CH:22][N:21]=1.[OH-].[K+]>CN1C(=O)CCC1>[CH3:1][N:2]1[C:15]2([CH2:17][CH2:16]2)[CH2:14][C:5]2[N:6]([CH2:27][CH2:26][C:23]3[CH:22]=[N:21][C:20]([C:19]([F:29])([F:18])[F:28])=[CH:25][CH:24]=3)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1
Reactant: C=Cc1ccc(C(F)(F)F)nc1
Reactant: Cc1ccc2[nH]c3c(c2c1)CN(C)C1(CC1)C3
Agent: [K+]
Agent: [OH-]
Solvent: CN1CCCC1=O
Product: Cc1ccc2c(c1)c1c(n2CCc2ccc(C(F)(F)F)nc2)CC2(CC2)N(C)C1

Procedure:
The title compound is prepared from a mixture of 2′,8′-dimethyl-1′,2′,4′,5′-tetrahydrospiro[cyclopropane-1,3′-pyrido[4,3-b]indole], 2-(trifluoromethyl)-5-vinylpyridine and KOH (5-7 equiv) in NMP at a temperature ranging between 25 deg C. to 100 deg C. The product obtained is isolated by preparative HPLC.
Reaction SMILES: [CH3:1][N:2]1[C:8](=[O:9])[C:7]2[CH:10]=[CH:11][CH:12]=[CH:13][C:6]=2[N:5]2[CH:14]=[N:15][C:16]([C:17](=[N:19][OH:20])[NH2:18])=[C:4]2[CH2:3]1.[Cl:21][CH2:22][C:23](OC(=O)CCl)=O>CN(C)C=O>[Cl:21][CH2:22][C:23]1[O:20][N:19]=[C:17]([C:16]2[N:15]=[CH:14][N:5]3[C:6]4[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=4[C:8](=[O:9])[N:2]([CH3:1])[CH2:3][C:4]=23)[N:18]=1
Reactant: O=C(CCl)OC(=O)CCl
Reactant: CN1Cc2c(C(N)=NO)ncn2-c2ccccc2C1=O
Solvent: CN(C)C=O
Product: CN1Cc2c(-c3noc(CCl)n3)ncn2-c2ccccc2C1=O
Yield: 70.5 %

Procedure:
4.60 g (16.95 mmol) 5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamidoxime were stirred with 3.19 g (18.65 mmol) of chloroacetic anhydride in 25 ml of N,N-dimethylformamide at room temperature for 30 minutes and at 105° for 2 hours. The reaction mixture was evaporated, the residue was dissolved in methylene chloride and the solution was washed with saturated sodium bicarbonate solution. After drying over magnesium sulfate the solution was concentrated and the crystalline residue was chromatographed on silica gel while eluting with ethyl acetate. There were obtained 3.94 g (70%) of 3-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-5,6-dihydro-5-methyl-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one of m.p. 208°-209°.
Reaction SMILES: [O:1]([NH:19][C:20](=[O:50])[CH2:21][C@@H:22]([N:33]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][C:41]([C:44]3[CH:49]=[CH:48][N:47]=[CH:46][CH:45]=3)=[CH:40][CH:39]=2)=[CH:34]1)[C:23]([NH:25][C@H:26]([CH2:31][OH:32])[C:27]([CH3:30])([CH3:29])[CH3:28])=[O:24])[Si](C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.P([O-])([O-])([O-])=O>C1COCC1>[CH3:28][C:27]([CH3:30])([CH3:29])[C@H:26]([NH:25][C:23](=[O:24])[C@H:22]([N:33]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][C:41]([C:44]3[CH:49]=[CH:48][N:47]=[CH:46][CH:45]=3)=[CH:40][CH:39]=2)=[CH:34]1)[CH2:21][C:20]([NH:19][OH:1])=[O:50])[CH2:31][OH:32]
Reactant: CC(C)(C)[C@@H](CO)NC(=O)[C@@H](CC(=O)NO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)n1ccc(-c2ccc(-c3ccncc3)cc2)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=P([O-])([O-])[O-]
Agent: [F-]
Solvent: C1CCOC1
Product: CC(C)(C)[C@@H](CO)NC(=O)[C@@H](CC(=O)NO)n1ccc(-c2ccc(-c3ccncc3)cc2)c1
Reaction time: 1.25 h
Yield: 41.6 %

Procedure:
To a solution of N4-t-butyldiphenylsiloxy-N1-[2,2-Dimethyl-1(S)-(hydroxymethyl)propyl]-2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamide (112 mg, 0.160 mmol) in THF (5 mL) was added a solution of tetra-n-butylammonium fluoride (0.20 mL of 1M in THF). After 1.25 hours at ambient temperature, the mixture was added dropwise to 1M pH7 phosphate buffer (40 mL). The resultant precipitate was collected by filtration and washed with H2O. A solution in CH2Cl2/MeOH was passed through a 0.45μ syringe filter, and the filtrate was concentrated to give a solid which was triturated with EtOH to yield 30 mg(42%) of N1-[2,2-Dimethyl-1(S)-(hydroxymethyl)propyl]-N4-hydroxy-2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamide as an amorphous solid, which decomposed>200° C. 1H NMR (CD3COOD): δ 8.91 (d, 2H, J=6.6 Hz), 8.23 (d, 2H, J=7.0 Hz), 7.93 (d, 2H, J=8.8 Hz), 7.76 (d, 2H, J=8.5 Hz), 7.42 (s, 1H), 6.95 (s, 1H), 6.60 (s, 1H), 5.44 (t, 1H, J=7.4 Hz), 3.92-3.88 (m, 2H), 3.63-3.55 (m, 1H), 3.21 (dd, 1H, J=6.4, 14.5 Hz), 3.03 (dd, 1H, J=8.1, 15.1 Hz), 0.93 (s, 9H). Anal: Calculated for C25H30N4O4.0.4H2O: C, 66.08; H, 6.96; N, 11.95. Found: C, 65.92; H, 6.79; N, 11.86.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[Cl:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C.O>[Cl:19][C:20]1[CH:25]=[C:24]([C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[CH2:10][C@H:9]3[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=2)[CH:23]=[CH:22][CH:21]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(Br)cc1
Reactant: OB(O)c1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(-c2cccc(Cl)c2)cc1
Temperature: 0 °C
Yield: 90.9 %

Procedure:
A solution of tert-butyl (trans)-2-(4-bromophenyl)cyclopropylcarbamate (Intermediate H, 3 g, 9.6 mmol), 3-chlorophenylboronic acid (1.8 g, 11.5 mmol) and K2CO3 (3.9 g, 28.8 mmol) in acetonitrile:water (4:1) was degassed for 20 min. Tetrakis triphenylphosphine palladium (300 mg) was added and heated at reflux for 18 h. After completion, the reaction mixture was poured into ice water (100 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with water (50 mL), brine (50 mL) and dried over anhydrous Na2SO4 filtered and evaporated. The crude residue was purified by column chromatography (SiO2) using EtOAc: Pet ether to give (3 g, 91%) tert-butyl (trans)-2-(3′-chlorobiphenyl-4-yl)cyclopropylcarbamate as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:11])[CH2:4][N:5]1[CH:9]=[C:8]([NH2:10])[N:7]=[CH:6]1.[F:12][C:13]1[CH:14]=[C:15]([CH2:20][C:21]([NH:23][CH:24]([CH2:28][CH2:29][CH3:30])[C:25](O)=[O:26])=[O:22])[CH:16]=[C:17]([F:19])[CH:18]=1>>[CH3:1][O:2][C:3](=[O:11])[CH2:4][N:5]1[CH:9]=[C:8]([NH:10][C:25](=[O:26])[CH:24]([NH:23][C:21](=[O:22])[CH2:20][C:15]2[CH:16]=[C:17]([F:19])[CH:18]=[C:13]([F:12])[CH:14]=2)[CH2:28][CH2:29][CH3:30])[N:7]=[CH:6]1
Reactant: COC(=O)Cn1cnc(N)c1
Reactant: CCCC(NC(=O)Cc1cc(F)cc(F)c1)C(=O)O
Product: CCCC(NC(=O)Cc1cc(F)cc(F)c1)C(=O)Nc1cn(CC(=O)OC)cn1

Procedure:
(4-Amino-imidazol-1-yl)-acetic acid methyl ester was coupled with 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid to afford the title compound: C13 NMR (100 MHz, CDCl3) 13.5, 19.1, 33.8, 42.3, 50.3, 53.6, 54.5, 102.2, 102.5, 102.7, 109.9, 112.4, 112.6, 130.0, 131.4, 139.0, 161.9, 164.2, 166.5, 171.4; MS m/z 409.1 (M+1).
Reaction SMILES: [Si]([O:18][C:19]1[CH:58]=[CH:57][C:22]([O:23][CH2:24][C@@H:25]([OH:56])[CH2:26][NH:27][CH2:28][CH2:29][C:30]2[CH:55]=[CH:54][C:33]([NH:34][CH:35]3[CH2:40][CH2:39][N:38]([C:41]([C:43]4[S:44][C:45]5[CH:53]=[CH:52][CH:51]=[CH:50][C:46]=5[C:47]=4[O:48][CH3:49])=[O:42])[CH2:37][CH2:36]3)=[CH:32][CH:31]=2)=[CH:21][CH:20]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C(Cl)(Cl)Cl.CO>[OH:56][C@H:25]([CH2:24][O:23][C:22]1[CH:21]=[CH:20][C:19]([OH:18])=[CH:58][CH:57]=1)[CH2:26][NH:27][CH2:28][CH2:29][C:30]1[CH:55]=[CH:54][C:33]([NH:34][CH:35]2[CH2:36][CH2:37][N:38]([C:41]([C:43]3[S:44][C:45]4[CH:53]=[CH:52][CH:51]=[CH:50][C:46]=4[C:47]=3[O:48][CH3:49])=[O:42])[CH2:39][CH2:40]2)=[CH:32][CH:31]=1
Reactant: COc1c(C(=O)N2CCC(Nc3ccc(CCNC[C@H](O)COc4ccc(O[Si](c5ccccc5)(c5ccccc5)C(C)(C)C)cc4)cc3)CC2)sc2ccccc12
Solvent: ClC(Cl)Cl
Solvent: CO
Product: COc1c(C(=O)N2CCC(Nc3ccc(CCNC[C@H](O)COc4ccc(O)cc4)cc3)CC2)sc2ccccc12
Yield: 83 %

Procedure:
{4-[4-(2-{[(2S)-3-(4-{[tert-Butyl(diphenyl)silyl]oxy}phenoxy)-2-hydroxypropyl]amino}ethyl)anilino]-1-piperidinyl}(3-methoxy-1-benzothiophen-2-yl)methanone (0.148 g, 0.182 mmol) was reacted according to Procedure H (eluant: 5:1 chloroform-methanol) to give the title compound (0.087 g, 0.151 mmol).
Reaction SMILES: [C:1]1([C@@H:7]([C@H:9]([C:11]([OH:13])=[O:12])[OH:10])[NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.C(=O)(O)[O-].[Na+].[C:20](Cl)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O.ClCCl>[C:20]([NH:8][C@@H:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C@H:9]([C:11]([OH:13])=[O:12])[OH:10])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: N[C@@H](c1ccccc1)[C@@H](O)C(=O)O
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: O=C(N[C@@H](c1ccccc1)[C@@H](O)C(=O)O)c1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 72 %

Procedure:
To a solution of compound 5.HCl (219 mg, 1.00 mmol) in water (10 mL) containing sodium bicarbonate (500 mg, 5.95 mmol) was added a solution of benzoyl chloride (0.14 mL, 1.20 mmol) in dichloromethane (5.0 mL). The mixture was vigorously stirred for 16 h at room temperature. The reaction mixture was acidified with 0.1N HCl and the crude product was extracted with ethyl acetate (40 mL×3). The combined organic extracts were dried over anhydrous magnesium sulfate and concentrated in vacuo to dryness. The residue was purified on a short silica gel column using chloroform/methanol (2/1) as the eluant to give N-benzoyl-(2R,3S)-3-phenylisoserine (6) (205 mg, 72%) as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.O.[C:13]1(C)C=CC(S(O)(=O)=O)=C[CH:14]=1>C(O)C>[OH:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([O:11][CH2:13][CH3:14])=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: O=C(O)Cc1cccc(O)c1
Solvent: O
Solvent: CCO
Product: CCOC(=O)Cc1cccc(O)c1

Procedure:
A solution of 2-(3-Hydroxyphenyl)acetic acid (25 g, 164.31 mmol) and p-Toluenesulfonic acid monohydrate (3.49 g, 18.3 mmol) in abs ethanol (250 ml) was refluxed for 4 hours or until all the starting material is consumed. The reaction mixture was concentrated, diluted with ethyl acetate and washed with water. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1) to give the title compound.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](OS(C(F)(F)F)(=O)=O)[C:5]([C:16]#[N:17])=[C:4]([C:18]2[O:19][CH:20]=[CH:21][CH:22]=2)[N:3]=1.[CH:23]([Sn](CCCC)(CCCC)CCCC)=[CH2:24].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[NH2:1][C:2]1[N:3]=[C:4]([C:18]2[O:19][CH:20]=[CH:21][CH:22]=2)[C:5]([C:16]#[N:17])=[C:6]([CH:23]=[CH2:24])[N:7]=1
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: N#Cc1c(OS(=O)(=O)C(F)(F)F)nc(N)nc1-c1ccco1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: C=Cc1nc(N)nc(-c2ccco2)c1C#N
Yield: 3.8 %

Procedure:
To a stirred solution of 250 mg (0.75 mmol) trifluoromethanesulfonic acid 2-amino-5-cyano-6-furan-2-yl-pyrimidin-4-yl ester in 15 ml dioxane under argon at room temperature were added 0.22 ml (0.75 mmol) vinyltributylstannane, 86 mg (0.07 mmol) tetrakis(triphenyl-phosphine)palladium(O) and 1.5 ml (3.0 mmol) 2M aqueous sodium carbonate solution. The reaction mixture was heated at reflux for 16 h, then concentrated in vacuo. The residue was partitioned between ethyl acetate and water and the organic phase washed with brine, dried over sodium sulfate, and concentrated in vacuo. Flash chromatography (1/1 ethyl acetate/hexane) followed by trituration in ether afforded 6 mg (4%) 2-amino-4-furan-2-yl-6-vinyl-pyrimidine-5-carbonitrile as a white crystalline solid. ES-MS m/e (%): 213 (M+H+, 100). Also obtained (as a by-product) was 3 mg (2%) 2-amino-4-ethyl-6-furan-2-yl-pyrimidine-5-carbonitrile as a yellow crystalline solid. ES-MS m/e (%): 215 (M+H+, 100).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4](Cl)=[O:5].[NH2:12][C:13]1[S:14][C:15]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:16]=2[N:17]=1.O1CCCC1>C(N(CC)CC)C>[F:25][C:22]([F:23])([F:24])[C:20]1[CH:19]=[CH:18][C:16]2[N:17]=[C:13]([NH:12][C:4](=[O:5])[C:3]3[C:2]([F:1])=[CH:10][CH:9]=[CH:8][C:7]=3[F:11])[S:14][C:15]=2[CH:21]=1
Reactant: O=C(Cl)c1c(F)cccc1F
Reactant: Nc1nc2ccc(C(F)(F)F)cc2s1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(Nc1nc2ccc(C(F)(F)F)cc2s1)c1c(F)cccc1F
Temperature: 35 °C
Reaction time: 5 h
Yield: 78.2 %

Procedure:
At 0 to 5° C., 2,6-difluorobenzoyl chloride (1.77 g) was added dropwise to a solution composed of 2-amino-6-trifluoromethylbenzothiazole (2.18 g), tetrahydrofuran (30 ml) and triethylamine (1.1 g). The reaction mixture was stirred at 30 to 40° C. for 5 hours, and then tetrahydrofuran was evaporated. The solid residue was washed with water and recrystallized from ethanol to give the desired N-(6-trifluoromethylbenzothiazol-2-yl)-2,6-difluorobenzamide (2.8 g).
Reaction SMILES: [F:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:3]=1[C:4]([N:6]=[C:7]=[O:8])=[O:5].[Cl:14][C:15]1[CH:16]=[C:17]([NH2:29])[CH:18]=[C:19]([Cl:28])[C:20]=1[O:21][C:22]([F:27])([F:26])[CH:23]([Cl:25])[F:24]>C1(C)C=CC=CC=1>[Cl:14][C:15]1[CH:16]=[C:17]([NH:29][C:7]([NH:6][C:4](=[O:5])[C:3]2[C:2]([F:1])=[CH:12][CH:11]=[CH:10][C:9]=2[F:13])=[O:8])[CH:18]=[C:19]([Cl:28])[C:20]=1[O:21][C:22]([F:27])([F:26])[CH:23]([Cl:25])[F:24]
Reactant: O=C=NC(=O)c1c(F)cccc1F
Reactant: Nc1cc(Cl)c(OC(F)(F)C(F)Cl)c(Cl)c1
Solvent: Cc1ccccc1
Product: O=C(NC(=O)c1c(F)cccc1F)Nc1cc(Cl)c(OC(F)(F)C(F)Cl)c(Cl)c1
Reaction time: 1 h
Yield: 57.9 %

Procedure:
2,6-Difluorobenzoyl isocyanate (5.5 g, 0.03 mole) was added to a solution of 3,5-dichloro-4-(2-chloro-1,1,2-trifluoroethoxy)benzenamine (8.8 g, 0.03 mole) in 150 ml toluene and heated under reflux with stirring for one hour giving a clear solution. Toluene was removed by evaporation in a rotary evaporator. The residue was recrystallized from aqueous acetic acid and then from acetonitrile giving a white solid (8.3 g, 58 percent yield), melting at 178°-180° C.
Reaction SMILES: [Cl:1]C1(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl.ClCl.[Cl:14][C:15]1[C:19]([F:21])([F:20])[C:18]([Cl:23])(F)[C:17]([F:25])([F:24])[C:16]=1[Cl:26]>>[Cl:14][C:15]1[C:19]([F:21])([F:20])[C:18]([Cl:1])([Cl:23])[C:17]([F:25])([F:24])[C:16]=1[Cl:26]
Reactant: FC1(F)C(Cl)=C(Cl)C(F)(F)C1(F)Cl
Reactant: ClC1=C(Cl)C(Cl)(Cl)C(Cl)=C1Cl
Agent: ClCl
Product: FC1(F)C(Cl)=C(Cl)C(F)(F)C1(Cl)Cl
Temperature: 0 °C
Yield: 9.7 %

Procedure:
200 g of HF were passed over 140 ml of this catalyst at 360° C. in the course of 6 hours. 102 g of hexachlorocyclopentadiene, 170 g of HF and 23 g of chlorine were then passed over at 350° C. in the course of 5 hours. The reaction gases were condensed in ice-water. 85.4 g of an organic phase which contained 60.5% of 1,2-dichloro-3,3,4,4,5,5-pentafluorocyclopent-1-ene, 23.5% of 1,2,4-trichloro-3,3,4,5,5-pentafluorocyclopent-1-ene (and isomers as in Example 1) and 9.7% of 1,2,4,4-tetrachloro-3,3,5,5-tetrafluorocyclopent-1-ene (and isomers as in Example 1) were formed. The hexachlorocyclopentadiene content in the reaction product was 0.1%.
Reaction SMILES: [C:1]1([S-:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Na+].Cl[C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:11]=1[N+:17]([O-:19])=[O:18]>CN(C=O)C.C(Cl)Cl>[CH3:16][C:13]1[CH:14]=[CH:15][C:10]([S:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[C:11]([N+:17]([O-:19])=[O:18])[CH:12]=1
Reactant: [S-]c1ccccc1
Reactant: Cc1ccc(Cl)c([N+](=O)[O-])c1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: Cc1ccc(Sc2ccccc2)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 87.4 %

Procedure:
A solution of sodium thiophenolate (3.96 g, 30 mmol) in 60 mL of DMF was heated at 50° C. with 4-chloro-3-nitrotoluene (2.65 mL, 20 mmol) with stirring for 2 days. Cooled to room temperature and diluted with CH2Cl2. Washed with water and dried the organic layer over Na2SO4. Filtered and concentrated under vacuum giving the title compound (4.29 g, 87%) 1H NMR (300 MHz, CDCl3) δ ppm: 2.36 (s, 3 H) 6.76 (d, J=8.09 Hz, 1 H) 7.16 (d, J=8.46 Hz, 1H) 7.45 (m, 3 H) 7.58 (m, 2 H) 8.03 (s, 1 H).
Reaction SMILES: [Cl:1][C:2]1[C:10]([OH:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.ON1C2C=CC=CC=2N=N1.[C:22]12([CH2:32][NH2:33])[CH2:31][CH:26]3[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]3)[CH2:23]1)[CH2:29]2.C1(N=C=NC2CCCCC2)CCCCC1>>[Cl:1][C:2]1[C:10]([OH:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:33][CH2:32][C:22]12[CH2:31][CH:26]3[CH2:25][CH:24]([CH2:30][CH:28]([CH2:27]3)[CH2:29]1)[CH2:23]2)=[O:6]
Reactant: NCC12CC3CC(CC(C3)C1)C2
Reactant: O=C(O)c1cccc(O)c1Cl
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Product: O=C(NCC12CC3CC(CC(C3)C1)C2)c1cccc(O)c1Cl

Procedure:
Prepared according to the method of Example 38 using 2chloro-3-hydroxybenzoic acid (0.39 g), 1-hydroxy benzotriazole (0.31 g), 1-adamantanemethylamine (0.4 ml) and 1,3-dicyclo-hexylcarbodiimide (0.47 g) to yield the title compound as a white solid (0.29 g).
Reaction SMILES: [CH:1]1([NH:6][C:7]([NH2:9])=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[CH:11]([C:17]([CH3:19])=O)[C:12]([O:14][CH2:15][CH3:16])=[O:13]>>[CH:1]1([NH:6][C:7]2[O:8][C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:17]([CH3:19])[N:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: NC(=O)NC1CCCC1
Reactant: CCOC(=O)C(Cl)C(C)=O
Product: CCOC(=O)c1oc(NC2CCCC2)nc1C
Yield: 16.4 %

Procedure:
By the procedure of Example 4, 10 g (78 mmol) of cyclopentyl urea was reacted with 10.7 g (65 mmol) of ethyl 2-chloroacetoacetate at 140°-150° C. for 4 hours. The product was separated, then purified by Kugelrohr distillation (135° C. @ 0.5 mm Hg) and then recrystallized from hexane to yield 2.54 g of a light yellow solid product (m.p.=50°-52° C.) identified in Table I.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH2:10][CH2:9][CH2:8][N:7]([C:11]2[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=2[Cl:19])[C:6]=1SC)=O.[CH3:22][NH:23][NH2:24].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:19][C:12]1[CH:13]=[C:14]([CH3:18])[CH:15]=[C:16]([CH3:17])[C:11]=1[N:7]1[CH2:8][CH2:9][CH2:10][C:5]2[C:3](=[O:2])[N:23]([CH3:22])[NH:24][C:6]1=2
Reactant: CNN
Reactant: COC(=O)C1=C(SC)N(c2c(C)cc(C)cc2Cl)CCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: O
Product: Cc1cc(C)c(N2CCCc3c2[nH]n(C)c3=O)c(Cl)c1
Temperature: 130 °C
Reaction time: 24 h

Procedure:
1-(2-Chloro-4,6-dimethylphenyl)-2-methylsulfanyl-1,4,5,6-tetrahydropyridine-3-carboxylic acid methyl ester (4.99 g), methylhydrazine (16.4 mL), p-toluenesulfonic acid monohydrate (2.91 g), and methanol (75 mL) were combined in a glass vessel sealed with a Telfon™ screw cap. The reaction mixture was stirred in a 130° C. oil bath for 24 h, then cooled to room temperature and concentrated on the rotary evaporator. The residue was chromatographed on silica gel using a methanol/dichloromethane gradient to give 3.21 g of 7-(2-chloro-4,6-dimethylphenyl)-2-methyl-1,2,4,5,6,7-hexahydropyrazolo-[3,4-b]pyridin-3-one, mp 95.9-99.9° C.