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

HRID 64273노트

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HRID 64273 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 8895Cupric acetate촉매HCID 6344Dichloromethane용매2회HCID 57417360Sodium chloride; water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-413d1f8d11a54b59bba557856361943a
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447106B2

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