Diisopropylethylamine → HCID 11260495, compound

HRID 1175071Notes

Reaction equation

HRID 1175071 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[Cl:27][C:28]1[C:29]([F:54])=[C:30]([NH:34][C:35]2[C:44]3[C:39](=[CH:40][C:41]([O:47][CH:48]4[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]4)=[C:42]([O:45][CH3:46])[CH:43]=3)[N:38]=[CH:37][N:36]=2)[CH:31]=[CH:32][CH:33]=1.C(N(C(C)C)CC)(C)C.[O:64]1[C:68]([C:69](O)=[O:70])=[CH:67][CH:66]=[N:65]1>C(Cl)Cl>[Cl:27][C:28]1[C:29]([F:54])=[C:30]([NH:34][C:35]2[C:44]3[C:39](=[CH:40][C:41]([O:47][CH:48]4[CH2:53][CH2:52][N:51]([C:69]([C:68]5[O:64][N:65]=[CH:66][CH:67]=5)=[O:70])[CH2:50][CH2:49]4)=[C:42]([O:45][CH3:46])[CH:43]=3)[N:38]=[CH:37][N:36]=2)[CH:31]=[CH:32][CH:33]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 20605991,2-Oxazole-5-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67415388HCID 67415388, compound

Product 1

HCID 11260495HCID 11260495, compoundYield 14.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

HATU (0.31 g) was added to a solution of N-(3-chloro-2-fluorophenyl)-6-methoxy-7-(piperidin-4-yloxy)quinazolin-4-amine dihydrochloride (300 mg), diisopropylethylamine (0.45 ml) and isoxazole-5-carboxylic acid (0.110 g) in methylene chloride (9 ml). The resulting mixture was stirred at room temperature for 2.5 hrs. Methylene chloride (20 ml) was added and the organics washed with aqueous sodium hydroxide (2M, 30 ml) and water (30 ml). The crudes were then purified by flash column chromatography eluting with methanol/methylene chloride (2.5/97.5). Fractions containing the desired product were evaporated to a white foam which was triturated with diethyl ether (20 ml) to give N-(3-chloro-2-fluorophenyl)-7-{[1-(isoxazol-5-ylcarbonyl)piperidin-4-yl]oxy}-6-methoxyquinazolin-4-amine as a white solid (0.045 g). 1H NMR Spectrum: (DMSO d6 373K) 1.86 (m, 2H), 2.10 (m, 2H), 3.59 (m, 2H), 3.88 (m, 2H), 3.98 (s, 3H), 4.92 (m, 1H), 6.87 (s, 1H), 7.26 (m, 1H), 7.38 (s, 1H), 7.42 (m, 1H), 7.59 (m, 1H), 7.83 (s, 1H), 8.39 (s, 1H), 8.62 (s, 1H), 9.30 (br s, 1H); Mass Spectrum: (M+H)+ 498.

Workup

  1. washthe organics washed with aqueous sodium hydroxide (2M, 30 ml) and water (30 ml)
  2. customThe crudes were then purified by flash column chromatography
  3. washeluting with methanol/methylene chloride (2.5/97.5)
  4. additionFractions containing the desired product
  5. customwere evaporated to a white foam which
  6. customwas triturated with diethyl ether (20 ml)

Sources & evidence

ORD record
ord-3aa5e5074d4e4fa1a3aef9a636b224c4
Source dataset
uspto-grants-2010_11
Patent number
US07838530B2

Reaction notes

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