Potassium Carbonate → HCID 71571660, compound

HRID 712424Notes

Reaction equation

HRID 712424 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]2[CH2:14][N:15]([CH2:17][CH2:18][CH2:19]Cl)[CH2:16][CH:9]12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[Cl:27][C:28]1[CH:29]=[C:30]([NH:35][C:36]2[C:45]3[C:40](=[CH:41][C:42]([O:47][CH3:48])=[C:43]([OH:46])[CH:44]=3)[N:39]=[CH:38][N:37]=2)[CH:31]=[CH:32][C:33]=1[F:34]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]2[CH2:14][N:15]([CH2:17][CH2:18][CH2:19][O:46][C:43]3[CH:44]=[C:45]4[C:40](=[CH:41][C:42]=3[O:47][CH3:48])[N:39]=[CH:38][N:37]=[C:36]4[NH:35][C:30]3[CH:31]=[CH:32][C:33]([F:34])=[C:28]([Cl:27])[CH:29]=3)[CH2:16][CH:9]12)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 104712174-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-olHCID 86729477HCID 86729477, compound

Product 1

HCID 71571660HCID 71571660, compoundYield 79.9%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-benzyl-6-(3-chloropropyl)octahydropyrrolo[3,4-b][1,4]oxazine (0.30 g) in DMF (5 mL) was added K2CO3 (0.59 g), 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.27 g) and tetrabutylammonium iodide (20 mg). The reaction mixture was heated at 90° C. for 18 h, cooled to room temperature. The mixture was diluted with CH2Cl2 (100 mL), washed with water (100 mL×3) and brine (100 mL), and dried over anhydrous Na2SO4. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to afford the title compound (390 mg, 79.59%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 579.1 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.07-2.09 (t, J=13.36 Hz, 2H), 2.09-2.10 (m, 1H), 2.40-2.43 (m, 1H), 2.66-2.68 (m, 2H), 2.70-2.78 (m, 2H), 3.00-3.02 (m, 1H), 3.08-3.13 (m, 1H), 3.65 (s, 3H), 3.77 (s, 1H), 3.99 (s, 3H), 4.02-4.04 (m, 1H), 4.20-4.22 (m, 2H), 5.30 (s, 1H), 7.13 (m, 1H), 7.26 (d, J=2.04 Hz, 1H), 7.30-7.31 (m, 1H), 7.56 (d, J=1.20 Hz, 5H), 7.81 (s, 1H), 7.90 (s, 1H), 7.92 (d, J=2.60 Hz, 1H), 8.64 (s, 1H) ppm.

Workup

  1. temperaturecooled to room temperature
  2. washwashed with water (100 mL×3) and brine (100 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationThe mixture was filtered
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH)

Sources & evidence

ORD record
ord-0ec3183c2e7245468f7f07d3a13f619a
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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