Potassium Carbonate → HCID 71572792, compound

HRID 712479Notes

Reaction equation

HRID 712479 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH2:8][CH:7]2[O:11][CH2:12][CH2:13][CH2:14][CH:6]12.C([O-])([O-])=O.[K+].[K+].[Cl:21][C:22]1[CH:23]=[C:24]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][C:36]([O:41][CH3:42])=[C:37]([OH:40])[CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH:25]=[CH:26][C:27]=1[F:28]>CN(C=O)C>[Cl:21][C:22]1[CH:23]=[C:24]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][C:36]([O:41][CH3:42])=[C:37]([O:40][CH2:2][CH2:3][CH2:4][N:5]4[CH2:10][CH2:9][CH2:8][CH:7]5[O:11][CH2:12][CH2:13][CH2:14][CH:6]45)[CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH:25]=[CH:26][C:27]=1[F:28]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 104712174-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-olHCID 86729496HCID 86729496, compound

Product 1

HCID 71572792HCID 71572792, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-(3-chloropropyl)octahydro-2H-pyrano[3,2-b]pyridine (0.23 g), K2CO3 (0.26 g) and 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.30 g) in 20 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 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 eluting agent: 20:1 (v/v) DCM/MeOH) to afford the title compound as a pale yellow solid (0.11 g, 25.00%), HPLC: 96.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 501.3 (M+1); 1H NMR (400 MHz, d6-DMSO) δ: 9.54 (s, 1H), 7.78 (d, J=4.0 Hz, 1H), 7.70 (t, J=8.0 Hz, 1H), 7.64 (s, 2H), 7.24 (d, J=4.2 Hz, 1H), 7.09 (t, J=8.0 Hz, 1H), 4.19 (m, 2H), 3.93 (s, 3H), 3.33-3.30 (m, 2H), 2.51-2.49 (m, 4H), 2.14-1.93 (m, 6H), 1.74-1.71 (m, 3H), 1.36-1.23 (m, 3H) ppm.

Workup

  1. temperaturecooled to rt
  2. extractionthe 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
  7. washeluting agent

Sources & evidence

ORD record
ord-372217f269f34cdf9d982940ab291b47
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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