Potassium Carbonate → HCID 71572225, compound

HRID 712450Notes

Reaction equation

HRID 712450 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([OH:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].C([O-])([O-])=O.[K+].[K+].Cl[CH2:30][CH2:31][CH2:32][N:33]1[CH2:38][CH2:37][C:36]2=[N:39][O:40][C:41]([CH3:42])=[C:35]2[CH2:34]1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([O:20][CH2:30][CH2:31][CH2:32][N:33]4[CH2:38][CH2:37][C:36]5=[N:39][O:40][C:41]([CH3:42])=[C:35]5[CH2:34]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 104712174-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-olHCID 86729489HCID 86729489, compound

Product 1

HCID 71572225HCID 71572225, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (1.20 g), K2CO3 (2.60 g) and 5-(3-chloropropyl)-3-methyl-4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridine (0.97 g) in 10 mL of DMF was stirred at 80° C. for 7 h, and treated with 250 mL of ice-water. Then the mixture was extracted with CH2Cl2 (50 mL×2). The combined organic phases were dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) DCM/MeOH) to give the title compound as a pale yellow solid (0.80 g, 45.00%), HPLC: 95.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 498.1 (M+1); 1H NMR (400 MHz, d6-DMSO) δ: 2.08 (m, J=4.0 Hz 2H), 2.51 (s, 3H), 2.70 (m, J=4.0 Hz, 6H), 2.37 (m, J=4.0 Hz, 2H), 3.94 (s, 3H), 4.20 (m, J=8.0 Hz, 2H), 7.21 (s, 1H), 7.42 (t, J=8.0 Hz, 1H), 7.44 (s, 2H), 8.11 (t, J=4.0 Hz, 1H), 8.50 (s, 1H) ppm.

Workup

  1. extractionThen the mixture was extracted with CH2Cl2 (50 mL×2)
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) DCM/MeOH)

Sources & evidence

ORD record
ord-76cadb250dbf44c1bfe07240f7db9853
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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