Diisopropylethylamine → 2,2-difluoro-N-(2-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-ylamino)phenyl)propanamide

HRID 1043587노트

반응식

HRID 1043587 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[N:10]=[C:11]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[C:12]2[N:18]=[C:17]([CH2:19][N:20]3[CH2:25][CH2:24][CH:23]([C:26]([OH:29])([CH3:28])[CH3:27])[CH2:22][CH2:21]3)[CH:16]=[CH:15][C:13]=2[N:14]=1.[F:36][C:37]([F:42])([CH3:41])[C:38](O)=[O:39].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:36][C:37]([F:42])([CH3:41])[C:38]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[N:10]=[C:11]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[C:12]2[N:18]=[C:17]([CH2:19][N:20]3[CH2:21][CH2:22][CH:23]([C:26]([OH:29])([CH3:28])[CH3:27])[CH2:24][CH2:25]3)[CH:16]=[CH:15][C:13]=2[N:14]=1)=[O:39]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 27828252,2-Difluoropropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 584049712-(1-((2-(2-Aminophenylamino)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol

생성물 1

HCID 584050242,2-difluoro-N-(2-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-ylamino)phenyl)propanamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

2-(1-((2-(2-aminophenylamino)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol was reacted with 2,2-difluoropropanoic acid (2 eq), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 1.5 eq) and DIPEA (4 eq) in DMF (4 mL) for 1 hr (hour). The reaction mixture was extracted with EtOAc and bicarbonate solution and the organic layer was dried with Magnesium sulfate, filtered, evaporated and purified via flash column chromatography to get 50 mg of 2,2-difluoro-N-(2-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-ylamino)phenyl)propanamide. This intermediate was reacted with acetic acid (1.6 mL) over one week to yield 4.1 mg of 120 following reverse phase HPLC purification. MS (Q1) 552.3 (M)+

후처리

  1. extractionThe reaction mixture was extracted with EtOAc and bicarbonate solution
  2. dry with materialthe organic layer was dried with Magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. custompurified via flash column chromatography

출처 및 근거

ORD 기록
ord-a59bd9ce41aa4208b6d559395dff04ba
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08563540B2

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