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 2091860ノート

反応式

HRID 2091860 の反応式
[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]

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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)+

後処理

  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

出典と根拠

ORDレコード
ord-06e31cb04708481caf90406543ebce7f
出典データセット
uspto-grants-2013_05
特許番号
US08440651B2

反応ノート

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