Potassium Carbonate → N-(3-chloro-4-fluorophenyl)-6-(3-(1-ethylhexahydro-1H-pyrrolo[3,4-b]pyridin-6(2H)-yl) propoxy)-7-methoxyquinazolin-4-amine

HRID 712491Notes

Reaction equation

HRID 712491 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:25][CH3:26])=[C:17]([O:20][CH2:21][CH2:22][CH2:23]Cl)[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+].[CH2:33]([N:35]1[CH2:40][CH2:39][CH2:38][CH:37]2[CH2:41][NH:42][CH2:43][CH:36]12)[CH3:34]>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:25][CH3:26])=[C:17]([O:20][CH2:21][CH2:22][CH2:23][N:42]4[CH2:41][CH:37]5[CH:36]([N:35]([CH2:33][CH3:34])[CH2:40][CH2:39][CH2:38]5)[CH2:43]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 50742265N-(3-Chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amineHCID 867295001-ethyloctahydro-1H-pyrrolo[3,4-b]pyridine

Product 1

HCID 71571661N-(3-chloro-4-fluorophenyl)-6-(3-(1-ethylhexahydro-1H-pyrrolo[3,4-b]pyridin-6(2H)-yl) propoxy)-7-methoxyquinazolin-4-amineYield 38.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of N-(3-chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine (1.50 g), K2CO3 (5.00 g) and 1-ethyloctahydro-1H-pyrrolo[3,4-b]pyridine (0.90 g) in 25 mL of DMF was stirred for 7 h at 80° C., and then cooled down. The resulted mixture was poured into 50 mL of ice-water and 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 give the title compound as a pale yellow solid (0.75 g, 38.60%), HPLC: 98.30%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 514.1 (M+1); 1H NMR (400 MHz, d6-DMSO) δ: 1.03 (t, J=4.6 Hz, 3H), 1.52-1.62 (m, 2H), 1.97-2.00 (m, 3H), 2.07-2.09 (m, 2H), 2.08-2.11 (m, 4H), 2.40 (q, J=4.6 Hz, 2H), 2.51-2.56 (m, 1H), 2.57-2.61 (m, 2H), 2.88-2.92 (m, 2H), 3.94 (s, 3H), 4.18 (t, J=8.6 Hz, 2H), 7.19 (s, 1H), 7.44 (t, J=10.4 Hz, 1H), 7.82 (s, 2H), 8.13 (t, J=6.8 Hz, 1H), 8.50 (s, 1H) ppm.

Workup

  1. temperaturecooled down
  2. extractionextracted 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 (eluting agent: 20:1 (v/v) DCM/MeOH)

Sources & evidence

ORD record
ord-d645b8668bbf460796caac56104af7d4
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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