Acetic Acid → 1-Acetyl-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide

HRID 1867748노트

반응식

HRID 1867748 반응식
C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:34](O)(=[O:36])[CH3:35].[Cl:38][C:39]1[C:40]([F:68])=[C:41]([NH:45][C:46]2[C:55]3[C:50](=[CH:51][C:52]([O:66][CH3:67])=[C:53]([CH2:56][N:57]([CH3:65])[C:58]4([C:62]([NH2:64])=[O:63])[CH2:61][NH:60][CH2:59]4)[CH:54]=3)[N:49]=[CH:48][N:47]=2)[CH:42]=[CH:43][CH:44]=1>ClCCl>[C:34]([N:60]1[CH2:61][C:58]([N:57]([CH2:56][C:53]2[CH:54]=[C:55]3[C:50](=[CH:51][C:52]=2[O:66][CH3:67])[N:49]=[CH:48][N:47]=[C:46]3[NH:45][C:41]2[CH:42]=[CH:43][CH:44]=[C:39]([Cl:38])[C:40]=2[F:68])[CH3:65])([C:62]([NH2:64])=[O:63])[CH2:59]1)(=[O:36])[CH3:35]

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579798103-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide

생성물 1

HCID 579798861-Acetyl-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide수율 51%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Diisopropylethylamine (0.11 ml, 0.63 mmol) and then HATU (95 mg, 0.25 mmol) were added to a solution of acetic acid (18 μl, 0.31 mmol) in dichloromethane (1 ml). After 10 minutes, the hydrochloride salt of 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide (100 mg, 0.21 mmol Example 74) was added and the mixture stirred overnight at room temperature. After removal of the solvent, the resulting product was dissolved in dimethylformamide and purified on preparative HPLC (standard basic conditions) to give the title product as a powder (52 mg, 51%); 1H NMR Spectrum: (CDCl3) 1.92 (d, 3H), 2.38 (s, 3H), 3.70 (d, 1H), 3.83 (d, 1H), 3.98 (s, 3H), 4.18-4.27 (m, 3H), 4.55 (d, 1H), 5.80 (brs, 1H), 6.94 (brs, 1H), 7.15 (m, 2H), 7.29 (s, 1H), 7.96 (brs, 2H), 8.34 (brs, 1H), 8.72 (s, 1H); Mass Spectrum: (M+H)+ 487.

후처리

  1. customAfter removal of the solvent
  2. dissolutionthe resulting product was dissolved in dimethylformamide
  3. custompurified on preparative HPLC (standard basic conditions)

출처 및 근거

ORD 기록
ord-493c91973ecf4b8a9ecc49240a0247a4
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07632840B2

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