Diisopropylethylamine → HCID 11261005, compound

HRID 1175070Notes

Reaction equation

HRID 1175070 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:52][CH3:53])=[C:42]([O:45][CH:46]4[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]4)[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.[CH3:64][C:65]1[CH:69]=[C:68]([CH2:70][C:71](O)=[O:72])[O:67][N:66]=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:52][CH3:53])=[C:42]([O:45][CH:46]4[CH2:47][CH2:48][N:49]([C:71](=[O:72])[CH2:70][C:68]5[O:67][N:66]=[C:65]([CH3:64])[CH:69]=5)[CH2:50][CH2:51]4)[CH:43]=3)[N:38]=[CH:37][N:36]=2)[CH:31]=[CH:32][CH:33]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 41955322-(3-Methyl-1,2-oxazol-5-yl)acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574768654-(3-Chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-4-yloxy)quinazoline dihydrochloride

Product 1

HCID 11261005HCID 11261005, compoundYield 81.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

HATU (0.31 g) was added to a solution of N-(3-chloro-2-fluorophenyl)-7-methoxy-6-(piperidin-4-yloxy)quinazolin-4-amine dihydrochloride (300 mg), diisopropylethylamine (0.45 ml) and 3-methyl-5-isoxazoleacetic Acid (0.135 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-methoxy-6-({1-[(3-methylisoxazol-5-yl)acetyl]piperidin-4-yl}oxy)quinazolin-4-amine as a white solid (0.269 g). 1H NMR Spectrum: (DMSO d6 373K) 1.79 (m, 2H), 1.98 (m, 2H), 2.23 (s, 3H), 3.50 (m, 2H), 3.79 (m, 2H), 3.92 (s, 2H), 3.97 (s, 3H), 4.77 (m, 1H), 6.18 (s, 1H), 7.24 (m, 2H), 7.42 (m, 1H), 7.59 (m, 1H), 7.89 (s, 1H), 8.39 (s, 1H), 9.28 (br s, 1H); Mass Spectrum: (M+H)+ 526.

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-03efc16d27b848aea900347777f9b6b4
Source dataset
uspto-grants-2010_11
Patent number
US07838530B2

Reaction notes

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