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

HRID 1867748ノート

反応式

HRID 1867748 の反応式
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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-493c91973ecf4b8a9ecc49240a0247a4
出典データセット
uspto-grants-2009_12
特許番号
US07632840B2

反応ノート

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