Potassium Carbonate → HCID 86729516, compound

HRID 712515Notes

Reaction equation

HRID 712515 reaction equation
[O:1]1[C@@H:6]2[CH2:7][NH:8][CH2:9][C@H:5]2[O:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[Cl:16][C:17]1[CH:18]=[C:19]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([O:40][CH3:41])=[C:32]([O:35][CH2:36][CH2:37][CH2:38]Cl)[CH:33]=3)[N:28]=[CH:27][N:26]=2)[CH:20]=[CH:21][C:22]=1[F:23]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[Cl:16][C:17]1[CH:18]=[C:19]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([O:40][CH3:41])=[C:32]([O:35][CH2:36][CH2:37][CH2:38][N:8]4[CH2:7][C@@H:6]5[O:1][CH2:2][CH2:3][O:4][C@H:5]5[CH2:9]4)[CH:33]=3)[N:28]=[CH:27][N:26]=2)[CH:20]=[CH:21][C:22]=1[F:23]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 50742265N-(3-Chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amineHCID 86729515HCID 86729515, compound

Product 1

HCID 86729516HCID 86729516, compoundYield 24.5%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (4aR,7aR)-hexahydro-2H-[1,4]dioxino[2,3-c]pyrrole (129.0 mg, 1.0 mmol), K2CO3 (217.0 mg, 1.56 mmol), tetrabutylammoniumiodide (44.0 mg, 0.12 mmol) and N-(3-chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine (475.0 mg, 1.20 mmol) in 15 mL of DMF was stirred for 9 h at 60° C., then poured into 10 mL of ice-water and extracted with CH2Cl2. 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 pale yellow solid (120 mg, 24.50%), HPLC: 94.43%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 489.9 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.04 (m, 2H), 2.6 (br, 1H), 2.72 (m, 2H), 2.82 (m, 2H), 3.04 (m, 2H), 3.64 (t, J=6.08 Hz, 2H), 3.80 (m, 4H), 3.98 (s, 3H), 4.16 (t, J=6.48 Hz, 2H), 7.14 (t, J=8.76 Hz, 1H), 7.23 (d, J=7.8 Hz, 1H), 7.58 (m, 2H), 7.90 (dd, J1=6.48 Hz, J2=2.56 Hz, 1H), 8.65 (s, 1H).

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialThe organic phase was dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was chromatographed with a silica gel column (eluting agent: 30:1 (v/v) DCM/MeOH)

Sources & evidence

ORD record
ord-bd8c3e2ab9da4cccb2e1c5711494cf4e
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

Loading…