Potassium Carbonate → tert-butyl 2-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy) propyl)hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate

HRID 712470Notes

Reaction equation

HRID 712470 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:21][CH3:22])=[C:17]([OH:20])[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+].Cl[CH2:30][CH2:31][CH2:32][N:33]1[CH2:41][CH:40]2[CH:35]([CH2:36][N:37]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:39]2)[CH2:34]1>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:21][CH3:22])=[C:17]([O:20][CH2:30][CH2:31][CH2:32][N:33]4[CH2:41][CH:40]5[CH:35]([CH2:36][N:37]([C:42]([O:44][C:45]([CH3:46])([CH3:48])[CH3:47])=[O:43])[CH2:38][CH2:39]5)[CH2:34]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 104712174-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-olHCID 86729494tert-butyl 2-(3-chloropropyl)hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate

Product 1

HCID 86729495tert-butyl 2-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy) propyl)hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylateYield 37.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.70 g), K2CO3 (0.61 g) and tert-butyl 2-(3-chloropropyl)hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate (0.80 g) in 30 mL of DMF was stirred at 80° C. for 7 h, then 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: 30:1 (v/v) DCM/MeOH) to give the title compound as colorless oil (0.48 g, 35.00%), HPLC: 95.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 587.2 (M+1); 1H NMR (400 MHz, d6-DMSO) δ: 1.45 (s, 9H), 1.99-2.06 (m, 4H), 2.32-2.38 (m, 2H), 2.46-2.50 (m, 4H), 2.67-2.71 (m, 2H), 3.40-3.45 (m, 2H), 4.17-4.19 (m, 2H), 4.19 (s, 3H), 4.20-2.26 (m, 2H), 7.21 (s, 1H), 7.42 (t, J=8.0 Hz, 1H), 7.44 (s, 2H), 7.78 (t, J=4.4 Hz, 1H), 8.50 (s, 1H) ppm.

Workup

  1. extractionextracted with CH2Cl2 (50 mL×3)
  2. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  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-b350f6bb43bb411a99b169569abcc3f7
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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