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

HRID 2091963ノート

反応式

HRID 2091963 の反応式
[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]

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 1234962-Acetoxyisobutyroyl chlorideHCID 168937Lithium hydroxide, monohydrateHCID 248780154-(4-aminophenyl)-N-(4-morpholinophenyl)pyrimidin-2-amine2 回

生成物 1

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

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-dedcbe424a794115b413d8194342b075
出典データセット
uspto-grants-2013_05
特許番号
US08440663B2

反応ノート

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