Potassium Carbonate → HCID 78116693, compound

HRID 712485Notes

Reaction equation

HRID 712485 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH:9]2[CH:7]([CH:8]2[N:11]([CH3:13])[CH3:12])[CH2:6]1.C([O-])([O-])=O.[K+].[K+].[Cl:20][C:21]1[CH:22]=[C:23]([NH:28][C:29]2[C:38]3[C:33](=[CH:34][C:35]([O:40][CH3:41])=[C:36]([OH:39])[CH:37]=3)[N:32]=[CH:31][N:30]=2)[CH:24]=[CH:25][C:26]=1[F:27]>CN(C=O)C>[Cl:20][C:21]1[CH:22]=[C:23]([NH:28][C:29]2[C:38]3[C:33](=[CH:34][C:35]([O:40][CH3:41])=[C:36]([O:39][CH2:2][CH2:3][CH2:4][N:5]4[CH2:10][CH:9]5[CH:7]([CH:8]5[N:11]([CH3:13])[CH3:12])[CH2:6]4)[CH:37]=3)[N:32]=[CH:31][N:30]=2)[CH:24]=[CH:25][C:26]=1[F:27]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 104712174-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-olHCID 86729497HCID 86729497, compound

Product 1

HCID 78116693HCID 78116693, compoundYield 44.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-(3-chloropropyl)-N,N-dimethyl-3-azabicyclo[3.1.0]hexan-6-amine (0.70 g), K2CO3 (0.78 g) and 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.70 g) in 30 mL of DMF was stirred at 80° C. for 7 h, and cooled to rt. To this, 50 mL of ice-water was added, and the resulted mixture was extracted with CH2Cl2 (50 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (diluting agent: 20:1 (v/v) DCM/MeOH) to give the title compound as a pale yellow solid (0.47 g, 35.00%), HPLC: 96.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 486.1 (M+1); 1H NMR (400 MHz, d6-DMSO) δ: 9.45 (s, 1H), 7.80 (d, J=4.0 Hz, 1H), 7.70 (t, J=8.0 Hz, 1H), 7.54 (s, 2H), 7.12 (d, J=4.2 Hz, 1H), 7.01 (t, J=8.0 Hz, 1H), 4.19-4.12 (m, 2H), 3.93 (s, 3H), 2.45-3.30 (m, 6H), 2.51 (s, 6H), 2.14-1.93 (m, 6H), 1.33 (m, 1H) ppm.

Workup

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

Sources & evidence

ORD record
ord-9b10a11e02334e8db8faa237e3808d1b
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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