Triethylamine → N-(4-(3-amino-4-hydroxycyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide

HRID 1523535노트

반응식

HRID 1523535 반응식
Br[C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][C:16]=2[CH:17]2[CH2:33][CH:21]3[N:22](C(OC(C)(C)C)=O)C(=O)[O:24][CH:20]3[CH2:19][CH2:18]2)=[O:9])[CH:5]=[CH:4][C:3]=1[F:34].[F:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[C:37]=1B(O)O.C(N(CC)CC)C>CCO.C1(C)C=CC=CC=1>[NH2:22][CH:21]1[CH:20]([OH:24])[CH2:19][CH2:18][CH:17]([C:16]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[NH:10][C:8](=[O:9])[C:6]2[CH:5]=[CH:4][C:3]([F:34])=[C:2]([C:37]3[C:36]([F:35])=[CH:41][CH:40]=[CH:39][C:38]=3[F:42])[N:7]=2)[CH2:33]1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 27343362,6-Difluorophenylboronic acidHCID 59226599tert-butyl 5-(3-(6-bromo-5-fluoropicolinamido)pyridin-4-yl)-2-oxohexahydrobenzo[d]oxazole-3(2H)-carboxylate

생성물 1

HCID 59226417N-(4-(3-amino-4-hydroxycyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide

시약·촉매·용매 1

HCID 21863594Toluene ethanol용매

실험 절차

A solution of tert-butyl 5-(3-(6-bromo-5-fluoropicolinamido)pyridin-4-yl)-2-oxohexahydrobenzo[d]oxazole-3(2H)-carboxylate (1.0 equiv), 2,6-difluorophenyl boronic acid (3.0 equiv.), tetrakistriphenylphosphine (0.2 equiv.) and triethylamine (3.0 equiv.) in 1:1 EtOH/toluene (0.1 M) was heated at 120° C. with microwave irradiation for 1200 seconds. Upon cooling, removal of the volatiles in vacuo, the Suzuki product was directly purified by reverse phase HPLC. The product fraction was lyophilized and the resulting cyclic carbamate and Boc groups were deprotected as described in Method 9 yielding, after RP HPLC purification and lyophilization, N-(4-(3-amino-4-hydroxycyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamideas the TFA salt. LCMS (m/z): 443.2 (MH+); LC Rt=2.11 min.

후처리

  1. temperatureUpon cooling
  2. customremoval of the volatiles in vacuo
  3. customthe Suzuki product was directly purified by reverse phase HPLC
  4. customafter RP HPLC purification and lyophilization, N-(4-(3-amino-4-hydroxycyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamideas the TFA salt

출처 및 근거

ORD 기록
ord-b14a9e6709f9445a9a3f1fc81bb373ac
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09079889B2

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