Benzyl chloroformate → Benzyl 2-(3-cyano-2-(4-hydroxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-7-yl)phenylcarbamate

HRID 64272

Reaction equation

HRID 64272 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[N:13]2[N:14]=[C:15]([C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)[C:16]([C:17]#[N:18])=[C:12]2[NH:11][CH2:10][CH2:9]1.C([O-])([O-])=O.[K+].[K+].[C:32](Cl)([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33]>C1COCC1>[C:17]([C:16]1[C:15]([C:19]2[CH:20]=[CH:21][C:22]([OH:25])=[CH:23][CH:24]=2)=[N:14][N:13]2[CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[NH:1][C:32](=[O:33])[O:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH2:9][CH2:10][NH:11][C:12]=12)#[N:18]

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 1369280897-(2-Aminophenyl)-2-(4-hydroxyphenyl)-4,5,6,7-tetrahydro pyrazolo[1,5-a]pyrimidine-3-carbonitrile

Product 1

HCID 136928069Benzyl 2-(3-cyano-2-(4-hydroxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-7-yl)phenylcarbamateYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 7-(2-aminophenyl)-2-(4-hydroxyphenyl)-4,5,6,7-tetrahydro pyrazolo[1,5-a]pyrimidine-3-carbonitrile (730 mg, 2.21 mmol) in THF (30 mL) was added K2CO3 (610 mg, 4.42 mmol), CbzCl (564 mg, 3.32 mmol). After stirring at 65° C. for 16 hr, the mixture was concentrated in vacuum. The residue was partitioned between 150 mL of DCM and 150 mL of brine. Organic layers were separated from aqueous layers, dried over Na2SO4 and purified by chromatography column on silica gel eluting with DCM/CH3OH to afford 370 mg (62%) of benzyl 2-(3-cyano-2-(4-hydroxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-7-yl)phenylcarbamate as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 9.71 (s, 1H), 9.33 (s, 1H), 7.66 (s, 1H), 7.58 (d, J=8.4 Hz, 2H), 7.44-7.28 (m, 7H), 7.17 (t, J=7.6 Hz, 1H), 6.79 (d, J=8.4 Hz, 2H), 6.59 (d, J=7.6 Hz, 1H), 5.82-5.77 (m, 1H), 5.17 (s, 2H), 3.25-3.18 (m, 1H), 2.97-2.87 (m, 1H), 2.36-2.24 (m, 1H), 2.08-2.00 (m, 1H).

Workup

  1. concentrationthe mixture was concentrated in vacuum
  2. customThe residue was partitioned between 150 mL of DCM and 150 mL of brine
  3. customOrganic layers were separated from aqueous layers
  4. dry with materialdried over Na2SO4
  5. custompurified by chromatography column on silica gel eluting with DCM/CH3OH

Sources & evidence

ORD record
ord-14947a583de24462bf6b469d35d9004a
Source dataset
uspto-grants-2016_09
Patent number
US09447106B2

Linked notes

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