Diisopropylethylamine → HCID 67417336, compound

HRID 1175076Notes

Reaction equation

HRID 1175076 reaction equation
CN(C([O:8]N1N=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.[CH3:64][C:65]1[CH:69]=[C:68]([CH2:70]C(O)=O)[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:47][CH:48]4[CH2:53][CH2:52][N:51]([C:70]([C:68]5[O:67][N:66]=[C:65]([CH3:64])[CH:69]=5)=[O:8])[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 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 67415388HCID 67415388, compound

Product 1

HCID 67417336HCID 67417336, compoundYield 69.4%

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 5 (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 (4/96). 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)-6-methoxy-7-({1-[(3-methylisoxazol-5-yl)carbonyl]piperidin-4-yl}oxy)quinazolin-4-amine as a white solid (0.224 g). 1H NMR Spectrum: (DMSO d6) 1.54-1.76 (m, 2H), 2.05 (m, 2H), 2.22 (s, 3H), 3.32 (m, 1H), 3.47 (m, 1H), 3.82 (m, 1H), 3.93 (m, 1H), 3.96 (s, 3H), 4.00 (s, 2H), 4.92 (m, 1H), 6.23 (s, 1H), 7.29 (m, 1H), 7.36 (s, 1H), 7.48 (m, 1H), 7.53 (m, 1H), 7.83 (s, 1H), 8.39 (s, 1H), 9.63 (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 (4/96)
  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-0ccd144cb33d45aeb4051e59c59bf3b5
Source dataset
uspto-grants-2010_11
Patent number
US07838530B2

Reaction notes

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