Triethylamine → 5-amino-N-(4-((1R,3S)-3-aminocyclohexyl)pyridin-3-yl)-3,3'-difluoro-2,4'-bipyridine-6-carboxamide

HRID 2046896노트

반응식

HRID 2046896 반응식
[NH2:1][C:2]1[C:3]([C:10]([NH:12][C:13]2[CH:14]=[N:15][CH:16]=[CH:17][C:18]=2[C@@H:19]2[CH2:24][CH2:23][CH2:22][C@H:21]([N:25]3C(=O)C4C(=CC=CC=4)C3=O)[CH2:20]2)=[O:11])=[N:4][C:5](Br)=[C:6]([F:8])[CH:7]=1.[F:36][C:37]1[CH:38]=[N:39][CH:40]=[CH:41][C:42]=1B(O)O.C(N(CC)CC)C>CCO.C1(C)C=CC=CC=1>[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([C:42]2[CH:41]=[CH:40][N:39]=[CH:38][C:37]=2[F:36])=[N:4][C:3]=1[C:10]([NH:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][C:18]=1[C@@H:19]1[CH2:24][CH2:23][CH2:22][C@H:21]([NH2:25])[CH2:20]1)=[O:11]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 27793533-Fluoropyridine-4-boronic acidHCID 86639734HCID 86639734, 화합물

생성물 1

HCID 461787745-amino-N-(4-((1R,3S)-3-aminocyclohexyl)pyridin-3-yl)-3,3'-difluoro-2,4'-bipyridine-6-carboxamide

시약·촉매·용매 1

HCID 21863594Toluene ethanol용매

실험 절차

A solution of 3-amino-6-bromo-N-(4-((1R,3S)-3-(1,3-dioxoisoindolin-2-yl)cyclohexyl)pyridin-3-yl)-5-fluoropicolinamide (1.0 equiv), 3-fluoropyridin-4-yl-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 phthalimide group was deprotected as described in Method 9 yielding, after RP HPLC purification and lyophilization, 5-amino-N-(4-((1R,3S)-3-aminocyclohexyl)-pyridin-3-yl)-3,3′-difluoro-2,4′-bipyridine-6-carboxamide as the TFA salt. LCMS (m/z): 425.1 (MH+); LC Rt=2.08 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, 5-amino-N-(4-((1R,3S)-3-aminocyclohexyl)-pyridin-3-yl)-3,3′-difluoro-2,4′-bipyridine-6-carboxamide as the TFA salt

출처 및 근거

ORD 기록
ord-1c8f914915574a8cb58b03c4111d7ae6
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08592455B2

반응 노트

불러오는 중…