Triethylamine → (R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-4-methylpentan-1-one

HRID 2062149ノート

反応式

HRID 2062149 の反応式
[N:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[OH:23])[N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[OH:31][C@H:32]([CH2:36][CH:37]([CH3:39])[CH3:38])[C:33](O)=[O:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[OH:31][C@H:32]([CH2:36][CH:37]([CH3:39])[CH3:38])[C:33]([N:4]1[CH2:3][CH2:2][N:1]([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[OH:23])[N:8]=2)[CH2:6][CH2:5]1)=[O:34]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 439960(R)-2-hydroxy-4-methylpentanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1361053622-(4-(Piperazin-1-yl)quinazolin-2-yl)phenol

生成物 1

HCID 135525571(R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-4-methylpentan-1-one収率 77%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 2-(4-(piperazin-1-yl)quinazolin-2-yl)phenol (250 mg, 0.82 mmol) in CH2Cl2 (6 mL) was added triethylamine (227 μL, 1.63 mmol) followed by the addition of (R)-2-hydroxy-4-methylpentanoic acid (140 mg, 1.06 mmol) and HATU (403 mg, 1.06 mmol). The reaction mixture was stirred at room temperature for 3 h and then quenched with H2O. The aqueous layer was extracted twice with CH2Cl2, dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 0-10% EtOAc in 50:50 CH2Cl2:hexanes gave (R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-4-methylpentan-1-one (265 mg, 77%). LC/MS: m/z 421.30 (M+H)+ at 2.57 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). H NMR (400 MHz, DMSO-d6) δ 8.47 (dd, J=8.3, 1.7 Hz, 1H), 8.12 (d, J=8.3 Hz, 1H) 7.88 (m, 2H), 7.57 (m, 1H), 7.40 (m, 1H), 6.96 (m, 2H), 4.92 (d, J=7.2 Hz, 1H), 4.39 (m, 1H), 3.95 (m, 4H), 3.76 (m, 4H), 1.80 (m, 1H), 1.43 (m, 2H), 0.92 (q, J=3.8 Hz, 6H).

後処理

  1. customquenched with H2O
  2. extractionThe aqueous layer was extracted twice with CH2Cl2
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via silica gel chromatography

出典と根拠

ORDレコード
ord-8953e2871e9448718bea76d05c7a5b4d
出典データセット
uspto-grants-2012_10
特許番号
US08283354B2

反応ノート

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