Potassium Carbonate → HCID 71572332, compound

HRID 712508Notes

Reaction equation

HRID 712508 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[CH2:38][CH2:37][C:36]2[N:39]([CH3:43])[N:40]=[C:41]([CH3:42])[C:35]=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[CH2:38][CH2:37][C:36]5[N:39]([CH3:43])[N:40]=[C:41]([CH3:42])[C:35]=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 86729509HCID 86729509, compound

Product 1

HCID 71572332HCID 71572332, compoundYield 244.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.50 g, 0.16 mmol, 1.0 eq) and K2CO3 (0.05 g, 0.32 mmol, 2.0 eq) in 20 mL of DMF was added 5-(3-chloropropyl)-1,3-dimethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine (0.05 g, 0.19 mmol, 1.2 eq) at room temperature. The reaction mixture was heated at 80° C. for 8.0 h and concentrated in vacuo. The residue was poured into a mixture of water (100 mL) and CH2Cl2 (150 mL). The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 30:1 (v/v) DCM/MeOH) to give the title compound as a yellow solid (0.20 g, 24.98%), HPLC: 95.21%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 513.02 (M+1); 1H NMR (400 MHz, d6-DMSO) δ: 1.91-2.08 (m, J=4.0 Hz 2H), 2.51 (s, 3H), 2.78 (s, 3H), 2.79-2.89 (m, 6H), 2.90-2.96 (m, 2H), 3.95 (s, 3H), 4.19 (m, 2H), 7.25 (s, 1H), 7.47 (t, J=8.12 Hz, 1H), 7.54 (s, 2H), 8.11 (t, J=5.16 Hz, 1H), 8.50 (s, 1H) ppm.

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe residue was poured into a mixture of water (100 mL) and CH2Cl2 (150 mL)
  3. dry with materialThe organic phase was dried over anhydrous Na2SO4
  4. concentrationconcentrated 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-94d118f244f64520b1d25b83b943e1f0
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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