Potassium Carbonate → N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)propoxy)quinazolin-4-amine

HRID 712381Notes

Reaction equation

HRID 712381 reaction equation
[C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[N:11]=[CH:10][N:9]=[C:8]2[NH:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[C:20]([Cl:25])[CH:19]=1)(=O)[CH3:2].C([O-])([O-])=O.[K+].[K+].ClCC[CH2:35][N:36]1[CH2:41][CH2:40][N:39]2[C:42]([C:45]([F:48])([F:47])[F:46])=[N:43][N:44]=[C:38]2[CH2:37]1>CN(C=O)C.O>[Cl:25][C:20]1[CH:19]=[C:18]([NH:17][C:8]2[C:7]3[C:12](=[CH:13][C:14]([O:15][CH3:16])=[C:5]([O:4][CH2:1][CH2:2][CH2:35][N:36]4[CH2:41][CH2:40][N:39]5[C:42]([C:45]([F:48])([F:46])[F:47])=[N:43][N:44]=[C:38]5[CH2:37]4)[CH:6]=3)[N:11]=[CH:10][N:9]=2)[CH:23]=[CH:22][C:21]=1[F:24]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 210983964-((3-Chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl acetateHCID 645803757-(3-Chloropropyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine

Product 1

HCID 71572223N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)propoxy)quinazolin-4-amineYield 45.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl acetate (0.62 g) and K2CO3 (0.35 g) in 10 mL of DMF was added 7-(3-chloropropyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (0.68 g) at rt. The reaction mixture was heated at 80° C. for 6 h, diluted with water and extracted with CH2Cl2. The combined organic phases were dried over anhydrous Na2SO4 for 1 h, and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 30:1 (v/v) DCM/MeOH) to give the title compound as a white solid (0.43 g, 40.00%), HPLC: 95.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 552.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.80 (m, 2H), 2.46 (t, J=4.2 Hz, 2H), 2.78 (t, J=3.6 Hz, 2H), 3.58 (s, 2H), 4.03 (s, 3H), 4.10 (t, J=4.2 Hz, 2H), 4.15 (t, J=3.6 Hz, 2H), 7.16 (s, 1H), 7.26 (s, 1H), 7.45 (s, 1H), 7.57 (m, 1H), 7.91 (m, 1H), 8.64 (s, 1H) ppm.

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialThe combined organic phases were dried over anhydrous Na2SO4 for 1 h
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was chromatographed with a silica gel column (eluting agent: 30:1 (v/v) DCM/MeOH)

Sources & evidence

ORD record
ord-b435594f478749c58efb387c97ca7df1
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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