Ethyl Acetate → (3-Methoxy-4-phenoxy-phenyl)-(6-piperidin-4-ylethynyl-quinazolin-4-yl)-amine

HRID 1264060Notes

Reaction equation

HRID 1264060 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[N:22]=[CH:21][N:20]=[C:19]3Cl)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.[CH3:28][O:29][C:30]1[CH:31]=[C:32]([CH:34]=[CH:35][C:36]=1[O:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[NH2:33].CCOC(C)=O>CC(O)(C)C.C(Cl)CCl.CO.Cl>[CH3:28][O:29][C:30]1[CH:31]=[C:32]([NH:33][C:19]2[C:18]3[C:23](=[CH:24][CH:25]=[C:16]([C:15]#[C:14][CH:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)[CH:17]=3)[N:22]=[CH:21][N:20]=2)[CH:34]=[CH:35][C:36]=1[O:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 155504831-Boc-4-(4-Chloroquinazolin-6-ylethynyl)piperidineHCID 186166313-Methoxy-4-phenoxyaniline hydrochloride

Product 1

HCID 15550484(3-Methoxy-4-phenoxy-phenyl)-(6-piperidin-4-ylethynyl-quinazolin-4-yl)-amineYield 76.7%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 21868497Tert-butyl alcohol 1,2-dichloroethaneSolvent

Procedure

A solution of 4-(4-chloro-quinazolin-6-ylethynyl)-piperidine-1-carboxylic acid tert-butyl ester (131 mg, 0.304 mmol) and 3-methoxy-4-phenoxyaniline hydrochloride (77 mg, 0.306 mmol) in tBuOH/ClCH2CH2Cl (1.0 /1.0 mL) was heated in a tightly capped reaction vial at 90° C. for 30 minutes. After cooling, the yellow mixture was diluted with MeOH and HCl gas was passed through the mixture for 10 minutes. After stirring for 2 hours, EtOAc was added to precipitate more solid which was collected by suction filtration, rinsed with EtOAc, and further dried to give 105 mg (66%) of yellow solid: 1H NMR (CD3OD) δ 1.93 -2.02 (m, 2H), 2.18 -2.24 (m, 2H), 3.12 -3.21 (m, 2H), 3.41 -3.47 (m, 2H), 3.81 (s, 3H), 6.87 (d, 2H), 7.02 (t, 1H), 7.06 (d, 1H), 7.27 (t, 2H), 7.33 (dd, 1H), 7.56 (d, 1H), 7.80 (d, 1H), 8.06 (d, 1H), 8.79 (s, 1H), 8.83 (s, 1H); MS m/z (MH+) 451.3.

Workup

  1. temperatureAfter cooling
  2. customto precipitate more solid which
  3. filtrationwas collected by suction filtration
  4. washrinsed with EtOAc
  5. customfurther dried

Sources & evidence

ORD record
ord-bb3530bb186748e88a32c51fe2835f02
Source dataset
uspto-grants-2003_04
Patent number
US06541481B2

Reaction notes

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