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

HRID 712464Notes

Reaction equation

HRID 712464 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[CH2:43][CH:42]2[CH:37]([NH:38][CH2:39][CH2:40][CH2:41]2)[CH2:36]1)[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:38]4[CH2:39][CH2:40][CH2:41][CH:42]5[CH2:43][N:35]([CH2:33][CH3:34])[CH2:36][CH:37]45)[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 545798326-Ethyloctahydro-1H-pyrrolo[3,4-b]pyridine

Product 1

HCID 71572441N-(3-chloro-4-fluorophenyl)-6-(3-(6-ethyloctahydro-1H-pyrrolo[3,4-b]pyridin-1-yl)propoxy)-7-methoxyquinazolin-4-amineYield 35%

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 (0.80 g), K2CO3 (3.00 g) and 6-ethyloctahydro-1H-pyrrolo[3,4-b]pyridine (0.40 g) in 25 mL of DMF was stirred at 80° C. for 7 h, then cooled to rt, 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 (0.36 g, 35.00%), HPLC: 95.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 515.4 (M+1); 1H NMR (400 MHz, d6-DMSO) δ: 1.93 (t, J=4.6 Hz, 3H), 2.21-2.33 (m, 4H), 2.43-2.50 (m, 5H), 2.54-2.60 (m, 2H), 2.98-3.02 (m, 2H), 3.17-3.20 (m, 3H), 3.35-3.41 (m, 1H), 3.48-3.52 (m, 1H), 4.29 (s, 3H), 4.34 (t, J=8.6 Hz, 2H), 7.20 (s, 1H), 7.41 (t, J=8.0 Hz, 1H), 7.43 (s, 2H), 7.91 (t, J=4.2 Hz, 1H), 8.47 (s, 1H) ppm.

Workup

  1. temperaturecooled to rt
  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-a8bc911a04294223b1ad6499b7ac0b36
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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