Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH:9]([CH2:12][CH2:13][CH3:14])[CH:10]=[CH2:11].CC1C=CC=CC=1[O-].[Li+].[CH2:24]1[CH2:28][O:27][CH2:26][CH2:25]1>>[CH3:28][O:27][C:26]1[CH:14]=[CH:13][C:12]([CH:9]([O:8][C:3]2[CH:2]=[CH:7][CH:6]=[CH:5][CH:4]=2)[CH:10]=[CH2:11])=[CH:24][CH:25]=1
Reactant: C1CCOC1
Reactant: C=CC(CCC)Oc1ccccc1C
Agent: Cc1ccccc1[O-]
Agent: [Li+]
Product: C=CC(Oc1ccccc1)c1ccc(OC)cc1
Reaction time: 20 h

Procedure:
(−)-1-Methyl-2-(1-propylallyloxy)benzene (Evans, P. A.; Leahy, D. K. J. Am. Chem. Soc. 2000, 122, 5012): The general procedure was followed with lithium 2-methylphenoxide (228 mg, 2.0 mmol) and 2-hexenyl methylcarbonate (160 mg, 1.0 mmol) in THF (2 mL). The reaction was conducted at 50° C. for 20 h. 1H NMR analysis of the mixture indicated the ratio of regioisomers to be 87/13. The residue was purified by flash chromatography on silica gel (0-1% Et2O/Hexanes) to afford 165 mg of the title compound as an oil. [86%, Rf 0.92 (5% Et2O/Hexanes)].[α]D20=−3.0 (c 0.3, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.16 (m, 2H), 6.88 (m, 2H), 5.92 (ddd, J=17.4, 10.5, 6.1 Hz, 1H), 5.28 (dt, J=17.4, 1.2 Hz, 1H), 5.22 (dt, J=10.5, 1.0 Hz, 1H), 4.67 (dt, J=6.4, 6.1 Hz, 1H), 2.31 (s, 3H), 1.89-1.83 (m, 1H), 1.76-1.69 (m, 1H), 1.60-1.47 (m, 2H), 1.01 (t, J=7.4 Hz, 3H); 13C NMR (125.77 MHz, CDCl3) δ 156.5 (C), 138.5 (CH), 130.6 (CH), 127.4 (C), 126.4 (CH), 120.2 (CH), 115.9 (CH2), 113.1 (CH), 78.6 (CH), 37.9 (CH2), 18.5 (CH2), 16.4 (CH3), 14.0 (CH3). HPLC analysis indicated an enantiomeric excess of 90% [Chiralcel® OD-H column, eluting with 99.9:0.1 hexane/i-PrOH, 0.6 mL/min, 220 nm; major enantiomer tR, 12.2, minor enantiomer tR 13.7 min].
Reaction SMILES: [CH3:1][N:2]([CH:12]1[CH:17]([CH3:18])[CH2:16][CH2:15][NH:14][CH2:13]1)[C:3]1[C:4]2[CH:11]=[CH:10][NH:9][C:5]=2[N:6]=[CH:7][N:8]=1.[C:19](Cl)(=[O:21])[CH3:20]>ClCCl.N1C=CC=CC=1>[CH3:18][CH:17]1[CH2:16][CH2:15][N:14]([C:19](=[O:21])[CH3:20])[CH2:13][CH:12]1[N:2]([CH3:1])[C:3]1[C:4]2[CH:11]=[CH:10][NH:9][C:5]=2[N:6]=[CH:7][N:8]=1
Reactant: CC1CCNCC1N(C)c1ncnc2[nH]ccc12
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)N1CCC(C)C(N(C)c2ncnc3[nH]ccc23)C1
Temperature: 25 °C
Reaction time: 18 h
Yield: 0 %

Procedure:
To a stirred solution of the product from Method C (0.03 grams, 0.114 mmol) dissolved in 5 mL of 10:1 dichloromethane/pyridine was added (0.018 grams, 0.228 mmol) of acetylchloride and the resulting mixture stirred at room temperature for 18 hours. The reaction mixture was then partitioned between dichloromethane and saturated sodium bicarbonate (NaHCO3). The organic layer was washed again with saturated NaHCO3, dried over sodium sulfate and concentrated to dryness in vacuo. The residue was purified by preparative thin layer chromatography (PTLC) (silica; 4% methanol in dichloromethane) affording 0.005 mg (15%) of the title compound as a colorless oil. LRMS: 288.1 (M+1).
Reaction SMILES: C([O:3][C:4](=[O:25])[CH:5]([C:18]1[CH:19]=[C:20]([CH3:24])[CH:21]=[CH:22][CH:23]=1)[CH2:6][C:7]#[C:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][CH:12]=1)=O)C.[NH2:26][NH2:27].C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.C(OCC)(=O)C>[Br:17][C:14]1[CH:13]=[CH:12][C:11]([C:9]2[N:27]([C:14]3[CH:15]=[CH:16][C:11]([CH3:9])=[CH:12][CH:13]=3)[N:26]=[C:7]([CH2:6][CH:5]([C:18]3[CH:19]=[C:20]([CH3:24])[CH:21]=[CH:22][CH:23]=3)[C:4]([OH:3])=[O:25])[CH:8]=2)=[CH:16][CH:15]=1
Reactant: CCOC(=O)C(CC#CC(=O)c1ccc(Br)cc1)c1cccc(C)c1
Reactant: NN
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1ccc(-n2nc(CC(C(=O)O)c3cccc(C)c3)cc2-c2ccc(Br)cc2)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 121.8 %

Procedure:
3-[5-(4-Bromo-phenyl)-1-β-tolyl-1H-pyrazol-3-yl]-2-m-tolyl-propionic acid ethyl ester. To a solution of 6-(4-bromo-phenyl)-6-oxo-2-m-tolyl-hex-4-ynoic acid ethyl ester (7.5 g, 19 mmol) in THF (40 mL) was added hydrazine (4.5 g, 28 mmol, 1.5 equiv) and Cs2CO3 (9.0 g, 28 mmol, 1.5 equiv). The reaction mixture was stirred at room temperature for 12 h. The resulting mixture was diluted with ethyl acetate (30 mL), and a satd aq solution of cesium carbonate (50 mL) was added. The resulting aqueous layer was back-extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with satd aq NaHCO3 (50 mL) then brine (50 mL), and dried (MgSO4). The solvent was evaporated under reduced pressure, and the residue was purified by chromatography (silica gel, 25% ethyl acetate/hexanes) to afford the desired compound (5.5 g, 58%). TLC (silica gel, 3:7 EtOAc/hexanes): Rf=0.35. MS (ESI): mass calculated for C28H27BrN2O2, 502.13; m/z found, 503/505 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.39 (d, J=10.7 Hz, 2H), 7.25-7.01 (m, 10H), 6.17 (s, 1H), 4.19-4.03 (m, 3H), 3.52 (dd, J=14.7, 9.6 Hz, 1H), 3.09 (dd, J=14.7, 6.0, 1H), 2.35 (s, 6H), 1.19 (t, J=7.1 Hz, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH:44]=[CH:43][C:5]2[CH:6]([C:16]3[C:17](=[O:42])[NH:18][C:19](=[O:41])[N:20]([C:22]4[N:27]=[C:26]([NH:28][CH2:29][C:30]([O:32]C(C)(C)C)=[O:31])[C:25]([C:37]([O:39][CH3:40])=[O:38])=[CH:24][N:23]=4)[CH:21]=3)[C:7]3[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:8]=3[CH:9]=[CH:10][C:4]=2[CH:3]=1.CO>FC(F)(F)C(O)=O.ClCCl>[CH3:15][C:12]1[CH:13]=[CH:14][C:7]2[CH:6]([C:16]3[C:17](=[O:42])[NH:18][C:19](=[O:41])[N:20]([C:22]4[N:27]=[C:26]([NH:28][CH2:29][C:30]([OH:32])=[O:31])[C:25]([C:37]([O:39][CH3:40])=[O:38])=[CH:24][N:23]=4)[CH:21]=3)[C:5]3[CH:43]=[CH:44][C:2]([CH3:1])=[CH:3][C:4]=3[CH:10]=[CH:9][C:8]=2[CH:11]=1
Reactant: COC(=O)c1cnc(-n2cc(C3c4ccc(C)cc4C=Cc4cc(C)ccc43)c(=O)[nH]c2=O)nc1NCC(=O)OC(C)(C)C
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)c1cnc(-n2cc(C3c4ccc(C)cc4C=Cc4cc(C)ccc43)c(=O)[nH]c2=O)nc1NCC(=O)O
Temperature: 25 °C
Reaction time: 5 h

Procedure:
A mixture of the product of step (iii) (0.57 g) in trifluoroacetic acid (5 ml) and dichloromethane (10 ml) was stirred at room temperature for 5 hours. Methanol (30 ml) was added and the precipitate collected. The solid was dissolved in methanol and sodium hydroxide solution and the product precipitated out by addition of 2M HCl. Yield 0.26 g.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]#[C:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])[CH:3]=1.[CH3:18][O:19][C:20](=[O:29])[CH2:21][C:22](=O)[CH2:23][C:24]([F:27])([F:26])[F:25].[CH3:30]C1C=CC(S(O)(=O)=O)=CC=1.O>>[CH2:18]([O:19][C:20]([C:21]1[C:22]([CH2:23][C:24]([F:27])([F:26])[F:25])=[N:8][C:5]2[C:4]([C:9]=1[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[Cl:17])=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)=[O:29])[CH3:30]
Reactant: Nc1ccc(Cl)cc1C#Cc1ccccc1Cl
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: COC(=O)CC(=O)CC(F)(F)F
Solvent: O
Product: CCOC(=O)c1c(CC(F)(F)F)nc2ccc(Cl)cc2c1Cc1ccccc1Cl

Procedure:
The title compound was prepared in analogy to example 10 step B from 4-chloro-2-(2-chloro-phenylethynyl)-phenylamine (prepared as described in example 10 step A, 300 mg, 1.14 mmol), 5,5,5-trifluoro-3-oxo-pentanoic acid methyl ester (prepared as described in example 34 step A, 421.4 mg, 2.29 mmol) and p-TsOH.H2O (326.54 mg, 1.72 mmol). Yellow solid (90 mg, 18% yield). LC-MS: 442 (M+H)+.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:25]=[CH:24][C:9]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)=[S:11])=[C:8]([OH:26])[CH:7]=1)[CH:2]1[O:4][CH2:3]1.[OH2:27]>O1CCCC1>[OH:4][CH:2]([CH2:3][OH:27])[CH2:1][O:5][C:6]1[CH:25]=[CH:24][C:9]([C:10]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:16][CH:17]=2)=[S:11])=[C:8]([OH:26])[CH:7]=1
Reactant: Oc1cc(OCC2CO2)ccc1C(=S)c1ccc(-c2ccccc2)cc1
Reactant: O
Solvent: C1CCOC1
Product: OCC(O)COc1ccc(C(=S)c2ccc(-c3ccccc3)cc2)c(O)c1

Procedure:
The title compound is prepared by the reaction of the compound of Example 14 with water in the presence of mineral acid in tetrahydrofuran.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[N:12]=[C:11]2[S:20][C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[CH:23][CH:22]=2)=[CH:6][CH:5]=1)([O-])=O.[Cl-].[Ca+2].[Cl-].O>C(O)C.[Fe]>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[N:12]=[C:11]2[S:20][C:21]2[CH:22]=[CH:23][C:24]([NH2:27])=[CH:25][CH:26]=2)=[CH:6][CH:5]=1
Reactant: CCOC(=O)c1cn(-c2ccc([N+](=O)[O-])cc2)c(Sc2ccc([N+](=O)[O-])cc2)n1
Agent: [Fe]
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CCO
Solvent: O
Product: CCOC(=O)c1cn(-c2ccc(N)cc2)c(Sc2ccc(N)cc2)n1
Yield: 77.9 %

Procedure:
Ethyl 1-(4-nitrophenyl)-2-[(4-nitrophenyl)thio]-1H-imidazole-4-carboxylate (3.00 g) was suspended in ethanol (120 mL), iron powder (4.05 g), anhydrous calcium chloride (0.81 g) and water (20 mL) were added, and the mixture was heated under reflux for 4 hr. The reaction mixture was allowed to cool, and filtered. Saturated aqueous sodium hydrogen carbonate solution was added to the obtained filtrate, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Methanol (30 mL) was added to the residue and the resulting crystals were collected by filtration to give the title compound as pale-yellow crystals (yield 2.00 g, 78%).
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:36])=[C:4]([CH3:35])[C:5]2[N:6]([C:8]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH:21]C(=O)OC(C)(C)C)[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.Cl.O1CCOCC1.[OH-].[Na+]>C(Cl)Cl.CO>[Cl:1][C:2]1[C:3]([CH3:36])=[C:4]([CH3:35])[C:5]2[N:6]([C:8]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([C:17]4([NH2:21])[CH2:18][CH2:19][CH2:20]4)=[CH:15][CH:16]=3)[N:10]=2)[N:7]=1
Reactant: Cc1c(Cl)nn2c(-c3ccccc3)c(-c3ccc(C4(NC(=O)OC(C)(C)C)CCC4)cc3)nc2c1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CO
Solvent: ClCCl
Product: Cc1c(Cl)nn2c(-c3ccccc3)c(-c3ccc(C4(N)CCC4)cc3)nc2c1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 44 %

Procedure:
To a mixture of the tert-butyl {1-[4-(6-chloro-7,8-dimethyl-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-32 (179 mg, 0.360 mmol, 1.0 eq) in DCM (2.29 mL) and MeOH (1.44 mL) was added a solution of 4 M hydrogen chloride in dioxane (1.78 mL, 7.12 mmol, 20.0 eq) and the mixture was stirred overnight at rt. The mixture was poured onto ice, made alkaline with aqueous sodium hydroxide (2 N) and extracted with DCM. The combined organic phases were washed with brine, dried and concentrated in vacuo. The crude mixture was purified via MPLC (Biotage Isolera; 10 g SNAP cartridge: DCM→DCM/ethanol 95/5) to give 64 mg (44% yield) of the title compound.
Reaction SMILES: [C:1]([OH:8])(=[O:7])[CH2:2][CH2:3][C:4]([CH3:6])=[O:5].[CH:9](=O)[C:10]1[O:14][CH:13]=[CH:12][CH:11]=1.S(=O)(=O)(O)O>C(O)=O>[C:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])(=[O:7])[CH2:2][CH2:3][C:4]([CH3:6])=[O:5].[CH:13]([O:8][CH2:1][CH2:2][CH2:3][CH2:4][CH3:6])=[O:14]
Reactant: O=Cc1ccco1
Reactant: CC(=O)CCC(=O)O
Agent: O=S(=O)(O)O
Solvent: O=CO
Product: CCCCCOC(=O)CCC(C)=O
Product: CCCCCOC=O

Procedure:
The liquid fraction comprises levulinic acid, formic acid, furfural, and sulphuric acid. The liquid fraction is supplied via line 8 to reactive extraction reactor 9. 1-pentanol, which may be fresh pentanol and/or recycled pentanol, is countercurrently supplied to reactor 9 via line 10. In reactive extraction reactor 9, levulinic acid and formic acid react with 1-pentanol to form pentyl levulinate and pentyl formate. The esters formed and furfural will be extracted to the organic, pentanol phase. Thus, an aqueous phase comprising sulphuric acid and an organic phase comprising 1-pentanol, pentyl levulinate, pentyl formate and furfural are formed. The organic, pentanol phase is discharged from reactor 9 via line 11 and may be separated into its individual components in a product separation section (see FIG. 2). The aqueous phase is discharged from reactor 9 via line 12 and for the greater part recycled to acid hydrolysis reaction zone 1 via line 13. Part of the aqueous phase is fed to extraction column 14 via line 15. 1-Pentanol is supplied to extraction column 14 via line 16. In column 14, the remainder of the organic compounds is extracted from the aqueous phase to yield a second aqueous phase that is removed from the process via line 17 and a second organic pentanol phase that is recycled to reactive extraction reactor 9 via line 18.
Reaction SMILES: C1(C)C=CC(S(O[CH2:11][CH2:12][C@@H:13]([CH3:20])[CH2:14][O:15][C:16]([CH3:19])([CH3:18])[CH3:17])(=O)=O)=CC=1.[CH2:22]([Mg]Br)[CH:23]([CH3:25])[CH3:24]>>[C:16]([O:15][CH2:14][C@H:13]([CH3:20])[CH2:12][CH2:11][CH2:22][CH:23]([CH3:25])[CH3:24])([CH3:17])([CH3:18])[CH3:19]
Reactant: CC(C)C[Mg]Br
Reactant: Cc1ccc(S(=O)(=O)OCC[C@@H](C)COC(C)(C)C)cc1
Product: CC(C)CCC[C@@H](C)COC(C)(C)C
Yield: 76 %

Procedure:
Coupling of (R)-(+)-4-tert. butoxy-3-methyl-1-butanol p-toluenesulfonate with isobutylmagnesium bromide was carried out using the procedure of Example 47. (R)-(+)-1-tert. Butoxy-2,6-dimethylheptane was obtained in 76% yield as a colorless liquid.
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][NH:10][C:11]([C:13]1[C:14]2[CH2:38][CH2:37][CH2:36][CH2:35][C:15]=2[S:16][C:17]=1[NH:18][C:19](=[O:34])[CH2:20][N:21]1[C:29]2[CH2:28][CH2:27][CH2:26][CH2:25][C:24]=2[C:23]([C:30]([F:33])([F:32])[F:31])=[N:22]1)=[O:12])(C)(C)C.C(N(CC)CC)C.[CH3:47][S:48](Cl)(=[O:50])=[O:49]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH3:47][S:48]([NH:7][CH2:8][CH2:9][NH:10][C:11]([C:13]1[C:14]2[CH2:38][CH2:37][CH2:36][CH2:35][C:15]=2[S:16][C:17]=1[NH:18][C:19](=[O:34])[CH2:20][N:21]1[C:29]2[CH2:28][CH2:27][CH2:26][CH2:25][C:24]=2[C:23]([C:30]([F:32])([F:33])[F:31])=[N:22]1)=[O:12])(=[O:50])=[O:49]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)NCCNC(=O)c1c(NC(=O)Cn2nc(C(F)(F)F)c3c2CCCC3)sc2c1CCCC2
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CS(=O)(=O)NCCNC(=O)c1c(NC(=O)Cn2nc(C(F)(F)F)c3c2CCCC3)sc2c1CCCC2
Temperature: 25 °C
Reaction time: 1 h
Yield: 25 %

Procedure:
[2-({2-[2-(3-Trifluoromethyl-4,5,6,7-tetrahydroindazol-1-yl)-acetylamino]-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonyl}-amino)-ethyl]-carbamic acid tert-butyl ester was dissolved in a solution of DCM (1 mL) and TFA (1 mL) and stirred at RT for 1 h, before concentration in vacuo. The resulting colourless oil was redissolved in DCM (1 mL) and triethylamine (7.70 μL, 0.055 mmol) added, followed by methanesulfonyl chloride (2.20 μL, 0.028 mmol). The resulting mixture was stirred at RT overnight. The sample was concentrated in vacuo and the residue obtained purified by preparative reverse phase HPLC to yield the title compound as a white solid (4 mg, 0.007 mmol, 25%).
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:5]2[S:10][C:9]([CH2:11][N:12]([CH3:16])[C:13](=[O:15])[CH3:14])=[CH:8][C:6]=2[N:7]=1.[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[C:24]1B(O)O>>[NH:23]1[C:31]2[C:26](=[C:27]([C:2]3[N:3]=[C:4]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:5]4[S:10][C:9]([CH2:11][N:12]([CH3:16])[C:13](=[O:15])[CH3:14])=[CH:8][C:6]=4[N:7]=3)[CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24]1
Reactant: OB(O)c1cc2ccccc2[nH]1
Reactant: CC(=O)N(C)Cc1cc2nc(Cl)nc(N3CCOCC3)c2s1
Product: CC(=O)N(C)Cc1cc2nc(-c3cccc4[nH]ccc34)nc(N3CCOCC3)c2s1

Procedure:
N-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-N-methyl-acetamide was reacted with indole boronic acid in general procedure A. Purification on silica yielded 193. NMR: 400MHz; CDCl3 2.10, 2.18 (3H,s,2 rotamers); 3.00 (3H,s); 3.84 (4H,m); 4.00 (4H,m); 4.73, 4.77 (2H,s,2 rotamers); 7.26 (2H,m); 7.33 (1H,s); 7.42 (1H,m); 7.48 (1H,s); 8.13 (1H,m); 8.21 (1H,br s). MS: (ESI+):M+H(422)
Reaction SMILES: Br[C:2]1[CH2:6][CH2:5][CH2:4][CH:3]=1.[Mg].[Br-].[CH3:9][C:10]1[O:15][CH2:14][N:13]([C:16]([CH3:20])([CH3:19])[CH:17]=[O:18])[C:12](=[O:21])[C:11]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl>O1CCCC1.BrCCBr.C(OCC)(=O)C>[CH3:9][C:10]1[O:15][CH2:14][N:13]([C:16]([CH3:19])([CH3:20])[CH:17]([C:2]2[CH2:6][CH2:5][CH2:4][CH:3]=2)[OH:18])[C:12](=[O:21])[C:11]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CC1=C(c2ccccc2)C(=O)N(C(C)(C)C=O)CO1
Reactant: BrC1=CCCC1
Agent: Cl
Agent: [Br-]
Agent: [Mg]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: BrCCBr
Product: CC1=C(c2ccccc2)C(=O)N(C(C)(C)C(O)C2=CCCC2)CO1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 98 %

Procedure:
A part of a solution of 1-bromocyclopent-1-ene (3.9 g) in tetrahydrofuran was added to a stirred mixture of magnesium turnings (0.68 g) and 1 drop of 1,2-dibromoethane in tetrahydrofuran at 20° C. under an inert atmosphere. The mixture was heated to reflux and the remaining bromide solution added dropwise over 15 minutes. The mixture was stirred for 0.5 hour, cooled to 0° C., and a solution of 2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropionaldehyde (4.0 g) in tetrahydrofuran added below 10° C. The mixture was stirred for 1 hour and ethyl acetate and hydrochloric acid (1N) added. The organic phase was washed (brine), dried (magnesium sulphate), evaporated and purified by silica gel column chromatography, eluting with n-hexane/ethyl acetate (2:1) to give 2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methyl-1-(cyclopent-1-enyl)propan-1-ol (4.95 g), NMR: 1.45(s,3H), 1.60(s,3H), 1.90(s,3H), 1.80-1.92(2H), 2.15-2.53(4H), 4.37(d,1H), 5.04(d,1H), 5.20-5.30(2H), 5.63(s,1H), 7.22-7.41(5H).
Reaction SMILES: [C:1]([NH:11][C@@H:12]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C@H:13]([OH:27])[CH:14](CC1C2C(=CC=CC=2)C=CC=1)[NH2:15])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(N([CH2:40][CH3:41])CC)C.C(O[C:46](=[O:48])[CH3:47])(=O)C>C1COCC1.CN(C1C=CN=CC=1)C>[C:1]([NH:11][C@@H:12]([CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[C@H:13]([OH:27])[CH2:14][N:15]([CH2:9][C:10]1[C:40]2[C:41](=[CH:28][CH:12]=[CH:13][CH:14]=2)[CH:7]=[CH:6][CH:5]=1)[C:46](=[O:48])[CH3:47])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]
Reactant: CCN(CC)CC
Reactant: CC(=O)OC(C)=O
Reactant: NC(Cc1cccc2ccccc12)[C@@H](O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Product: CC(=O)N(Cc1cccc2ccccc12)C[C@@H](O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1
Reaction time: 12 h

Procedure:
The Cbz protected amino alcohol (XVII) (0.035 g, 0.076 mmol) was dissolved in 1 ml of anhydrous THF. To this triethylamine (0.11 mmol) was added dropwise. After 10 minutes acetic anhydride (0.11 mmol) was added and 1 mg of DMAP was added. The reaction mixture was stirred for 12 hrs and it was then washed with water. The organic layer was separated, dried (Na2SO4), and concentrated under reduced pressure. It was then subjected to silca gel chromatography with 2:1 hexane/ethyl acetate as eluent to give the acetylated amino alcohol (XVIII) as an oil. 0.028 g (73%). 1H NMR (500 MHz, CDCl3) δ 7.80-8.06 (m, 2H), 7.13-7.49 (m, 15H), 5.02-5.37 (m, 3H), 4.52-4.87 (m, 2H), 3.75-4.00 (m, 2H), 3.28-3.51 (m, 1H), 2.75-2.94 (m, 2H), 2.07 (s, 3H). 13CNMR (125 MHz, CDCl3) 168.4, 155.85, 139.41, 139.36, 138.22, 135.43, 129.15, 128.68, 128.56, 128.37, 128.10, 127.72, 127.41, 127.64, 126.75, 125.62, 123.75, 80.23, 60.18, 54.14, 50.15, 47.99, 37.43, 17.1.
Reaction SMILES: [C:1]1([S:7]([CH2:10][C:11](=[O:13])[CH3:12])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14](Cl)/[CH:15]=[CH:16]/[CH2:17]Cl>>[C:1]1([S:7]([C:10]2([C:11](=[O:13])[CH3:12])[CH2:17][CH:16]2[CH:15]=[CH2:14])(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: ClC/C=C/CCl
Reactant: CC(=O)CS(=O)(=O)c1ccccc1
Product: C=CC1CC1(C(C)=O)S(=O)(=O)c1ccccc1

Procedure:
Utilizing a phase-transfer procedure similar to that described in Example I, phenylsulfonylacetone was reacted with 1,4-dichlorobutene-2 to obtain 1-phenylsulfonyl-1-acetyl-2-vinylcyclopropane. For the reaction, 9.91 grams phenylsulfonylacetone (Parish Chemical Co.) and 6.25 grams 1,4-dichlorobutene-2 were combined in 20 mls sulfolane containing 6.6 grams potassium hydroxide (85%) and 5 mole percent tricaprylylmethylammonium chloride. The reaction mixture was stirred at 35°-40° C. for 31/2 hours. One-hundred mls water was then added to dissolve the white granular precipitate which had formed and the mixture extracted several times with ether. A crude red oil (10.8 grams) was obtained after removal of the ether and further work-up utilizing a Waters Preparatory Liquid Chromatograph 500A equipped with a gel permeation column and operated at a flow rate of 0.1 l/min yielded the cis and trans isomers of 1-phenylsulfonyl-1-acetyl-2-vinylcyclopropane. ##STR18## trans 1-phenylsulfonyl-1-acetyl-2-vinylcyclopropane
Reaction SMILES: [NH2:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]([NH:8][CH:9]([CH3:20])[C:10]([N:12]2[CH2:16][CH2:15][CH2:14][CH:13]2[C:17]([OH:19])=O)=[O:11])=[O:7])=[CH:4][C:3]=1[Cl:23].C(OC(=O)[NH:29][CH:30]1[CH2:34][C:33](=[O:35])[O:32][CH:31]1[O:36][CH:37]([CH3:39])[CH3:38])C=C.O=C1OC(OCCC2C=CC=CC=2)C(NC(C2CCCN2C(=O)C(NC(=O)C2C=CC(N)=C(Cl)C=2)C)=O)C1>>[CH:37]([O:36][CH:31]1[CH:30]([NH:29][C:17]([CH:13]2[CH2:14][CH2:15][CH2:16][N:12]2[C:10](=[O:11])[CH:9]([NH:8][C:6](=[O:7])[C:5]2[CH:21]=[CH:22][C:2]([NH2:1])=[C:3]([Cl:23])[CH:4]=2)[CH3:20])=[O:19])[CH2:34][C:33](=[O:35])[O:32]1)([CH3:39])[CH3:38]
Reactant: CC(NC(=O)c1ccc(N)c(Cl)c1)C(=O)N1CCCC1C(=O)O
Reactant: C=CCOC(=O)NC1CC(=O)OC1OC(C)C
Agent: CC(NC(=O)c1ccc(N)c(Cl)c1)C(=O)N1CCCC1C(=O)NC1CC(=O)OC1OCCc1ccccc1
Product: CC(C)OC1OC(=O)CC1NC(=O)C1CCCN1C(=O)C(C)NC(=O)c1ccc(N)c(Cl)c1
Yield: 66 %

Procedure:
Prepared from 97a and (2-isopropoxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester according to the procedure used to prepare 98a to afford 200 mg of title compound (66% yield). 1H-NMR (500 MHz, 1:1 CDCl3:CD3OD) δ 1.05-1.35 (m, 6H), 1.35-1.50 (m, 3H), 1.70-2.45 (m, 4H), 2.45-3.05 (m, 2H), 3.55-4.10 (m, 3H), 4.15-4.88 (m, 4H), 5.48 (s, 0.4H), 5.58 (s, 0.1H), 5.64 (d, 0.4H), 5.70 (d, 0.1H), 6.78 (d, 1H), 7.58 (d, 1H), 7.80 (s, 1H). Analytical HPLC: 12.19, 12.40 min. LC-MS (ES+): m/e=581.2 (M+H+).
Reaction SMILES: [C:1]1([C:7]2[C:15]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH2:22])[CH:17]=3)=[C:10]3[NH:11][CH2:12][CH2:13][CH2:14][N:9]3[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:32])[CH3:31].O>O1CCCC1>[C:1]1([C:7]2[C:15]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:30](=[O:32])[CH3:31])[CH:17]=3)=[C:10]3[NH:11][CH2:12][CH2:13][CH2:14][N:9]3[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Nc1cc(-c2c(-c3ccccc3)nn3c2NCCC3)ccn1
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: CC(=O)Nc1cc(-c2c(-c3ccccc3)nn3c2NCCC3)ccn1
Temperature: 25 °C
Reaction time: 4 h
Yield: 12 %

Procedure:
To a solution of 4-(2-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)pyridin-2-amine (29 mg, 0.1 mmol, 1 eq) in 2 mL of tetrahydrofurane is added triethylamine (0.055 mL, 0.4 mmol, 4 eq) and then acetyl chloride (0.024 mL, 0.3 mmol, 3 eq). The mixture is stirred for 4 h at room temperature. Triethylamine (0.055 mL, 0.4 mmol, 4 eq) and acetyl chloride (0.024 mL, 0.3 mmol, 3 eq) are then added. The mixture is stirred overnight at room temperature and then poured into water and extracted with dichloromethane (3×50 mL). The combined organic layers are washed with a saturated solution of NaHCO3, brine, dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The crude material is purified by column chromatography using silica gel in heptane and ethyl acetate (1:0 to 0:1) as eluent and 4 mg (8%) of N-[4-(2-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)pyridin-2-yl]acetamide are obtained as a light brown oil.