Diisopropylethylamine → (R)-benzyl 3-hydroxy-1-(4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)phenylamino)-1-oxopropan-2-ylcarbamate

HRID 2091965노트

반응식

HRID 2091965 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[CH:17][CH:16]=3)[N:9]=2)=[CH:4][CH:3]=1.[C:27]([NH:37][C@@H:38]([C:41](O)=[O:42])[CH2:39][OH:40])([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(N(C)C)=O.CO.C(Cl)Cl.O>[OH:42][CH2:41][C@@H:38]([NH:37][C:27](=[O:28])[O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:39]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:16]=[CH:17][C:18]([N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)=[CH:19][CH:20]=3)[N:9]=2)=[CH:4][CH:3]=1)=[O:40]

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 489184Z-D-Ser-OHHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 248780154-(4-aminophenyl)-N-(4-morpholinophenyl)pyrimidin-2-amine

생성물 1

HCID 70271434(R)-benzyl 3-hydroxy-1-(4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)phenylamino)-1-oxopropan-2-ylcarbamate수율 78.3%

시약·촉매·용매 3

HCID 962Water용매HCID 31374Dimethylacetamide용매HCID 21226129Dichloromethane methanol용매

실험 절차

To a solution of 4-(4-aminophenyl)-N-(4-morpholinophenyl)pyrimidin-2-amine 249(a) (521 mg, 1.5 mmol), N-CBZ-D-Serine (359 mg, 1.5 mmol), and DIEA (0.653 mL, 3.75 mol) in DMA (4 mL) was added HATU (855 mg, 2.25 mmol) and the solution was stirred at room temperature for 0.5 hour. Excess H2O was added to the reaction mixture. The precipitate was collected and were redissolved in CH2Cl2, washed with NaHCO3 (aq) (2×), brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica column chromatography. (1% MeOH/DCM as eluent) to afford (R)-benzyl 3-hydroxy-1-(4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)phenylamino)-1-oxopropan-2-ylcarbamate 365(a) (668 mg, 78% yield).

후처리

  1. customThe precipitate was collected
  2. dissolutionwere redissolved in CH2Cl2
  3. washwashed with NaHCO3 (aq) (2×), brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica column chromatography

출처 및 근거

ORD 기록
ord-e83eac2661b7407188877f9bf35b7344
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08440663B2

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