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

HRID 64273Notes

Reaction equation

HRID 64273 reaction equation
[C:1]([C:3]1[C:4]([C:29]2[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=2)=[N:5][N:6]2[CH:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[NH:18][C:19](=[O:28])[O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:10][CH2:9][NH:8][C:7]=12)#[N:2].[F:36][C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1.CO>C(Cl)Cl.[Cl-].[Na+].O.CC([O-])=O.CC([O-])=O.[Cu+2]>[C:1]([C:3]1[C:4]([C:29]2[CH:30]=[CH:31][C:32]([O:35][C:40]3[CH:41]=[CH:42][C:37]([F:36])=[CH:38][CH:39]=3)=[CH:33][CH:34]=2)=[N:5][N:6]2[CH:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[NH:18][C:19](=[O:28])[O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:10][CH2:9][NH:8][C:7]=12)#[N:2]

Participants

7

Reactant 3

HCID 887MethanolHCID 2856454-Fluorophenylboronic acidHCID 136928069Benzyl 2-(3-cyano-2-(4-hydroxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-7-yl)phenylcarbamate

Product 1

HCID 136928063Benzyl 2-(3-cyano-2-(4-(4-fluorophenoxy)phenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-7-yl)phenylcarbamateYield 75%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of benzyl 2-(3-cyano-2-(4-hydroxyphenyl)-4,5,6,7-tetrahydro pyrazolo[1,5-a]pyrimidin-7-yl)phenylcarbamate (370 mg, 0.8 mmol) in 20 mL of DCM was added 4-fluorophenylboronic acid (167 mg, 1.2 mmol), TEA (162 mg, 1.6 mmol) and Cu(OAc)2 (216 mg, 1.2 mmol). After stirring at RT for 16 hr, 100 mL of DCM, 10 mL of CH3OH and 100 mL of brine were added to the mixture. Organic layers were separated from aqueous layers, washed with brine (100 mL×2), dried over Na2SO4 and purified by chromatography column on silica gel eluting with DCM/CH3OH to afford 334 mg (75%) of benzyl 2-(3-cyano-2-(4-(4-fluorophenoxy)phenyl)-4,5,6,7-tetrahydro pyrazolo[1,5-a]pyrimidin-7-yl)phenylcarbamate as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 7.76-7.74 (m, 3H), 7.45-7.10 (m, 12H), 7.02 (d, J=8.4 Hz, 2H), 6.59 (d, J=8.0 Hz, 1H), 5.85-5.80 (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. customOrganic layers were separated from aqueous layers
  2. washwashed with brine (100 mL×2)
  3. dry with materialdried over Na2SO4
  4. custompurified by chromatography column on silica gel eluting with DCM/CH3OH

Sources & evidence

ORD record
ord-413d1f8d11a54b59bba557856361943a
Source dataset
uspto-grants-2016_09
Patent number
US09447106B2

Reaction notes

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