Diisopropylethylamine → 2-hydroxy-2-methyl-N-(4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)phenyl)propanamide

HRID 2091963노트

반응식

HRID 2091963 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.CCN(C(C)C)C(C)C.C([O:39][C:40]([CH3:45])([CH3:44])[C:41](Cl)=[O:42])(=O)C.O[Li].O>CC(N(C)C)=O.O.CCOC(C)=O>[OH:39][C:40]([CH3:45])([CH3:44])[C:41]([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:42]

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 1234962-Acetoxyisobutyroyl chlorideHCID 168937Lithium hydroxide, monohydrateHCID 248780154-(4-aminophenyl)-N-(4-morpholinophenyl)pyrimidin-2-amine2회

생성물 1

HCID 579912222-hydroxy-2-methyl-N-(4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)phenyl)propanamide수율 85%

시약·촉매·용매 3

HCID 962Water용매2회HCID 8857Ethyl Acetate용매HCID 31374Dimethylacetamide용매

실험 절차

To a solution of 4-(4-aminophenyl)-N-(4-morpholinophenyl)pyrimidin-2-amine (1.0 g, 2.8 mol) 249(a) and DIPEA (0.5 mL, 1 eq.) in anhydrous DMA (5 mL) was added dropwise 2-acetoxy-2-methylpropionyl chloride (3 mol, 1.05 eq., 0.44 mL) at 0° C. The mixture was stirred for 20 min at room temperature. The solution was diluted with water and EtOAc. The organic layer was concentrated in vacuo. The residue 366(a) was suspended in MeOH (10 mL) and a solution of LiOH—H2O (8.3 mmol, 3 eq. 0.35 g) in water (3 mL) was added. The reaction was complete within 20 min and then was neutralized. The organic solvent was removed in vacuo. The residue was purified to afford 2-hydroxy-2-methyl-N-(4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)phenyl)propanamide (366) (1.0 g, 85% yield) as a pale yellow solid. 1H-NMR (400 MHz, DMSO-d6): 9.86 (s, 1H), 9.41 (s, 1H), 8.47 (d, 1H), 8.12 (d, 2H), 7.94 (d, 2H), 7.68 (d, 2H), 7.30 pm (d, 1H), 6.94 (d, 2H), 5.82 (s, 1H), 3.75 (m, 4H), 3.08 (m, 4H), 1.38 (s, 6H); MS (EI) m/z for C22H23N5O3HCl: 434.2 (MH+).

후처리

  1. concentrationThe organic layer was concentrated in vacuo
  2. waitThe reaction was complete within 20 min
  3. customThe organic solvent was removed in vacuo
  4. customThe residue was purified

출처 및 근거

ORD 기록
ord-dedcbe424a794115b413d8194342b075
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08440663B2

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