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

HRID 1867748Notes

Reaction equation

HRID 1867748 reaction equation
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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-493c91973ecf4b8a9ecc49240a0247a4
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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