Dichloromethane → N-(3-ethynylphenyl)-6-(3-(hexahydrofuro[3,4-c]pyridin-5(3H)-yl)propoxy)-7-methoxyquinazolin-4-amine

HRID 712523Notes

Reaction equation

HRID 712523 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([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:6]=[CH:7][CH:8]=1)#[CH:2].Cl[CH2:24][CH2:25][CH2:26][N:27]1[CH2:32][CH2:31][CH:30]2[CH2:33][O:34][CH2:35][CH:29]2[CH2:28]1.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([O:20][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][CH:30]5[CH2:33][O:34][CH2:35][CH:29]5[CH2:28]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1)#[CH:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 219252124-(3-Ethynylphenylamino)-7-methoxyquinazolin-6-olHCID 867295055-(3-Chloropropyl)octahydrofuro[3,4-c]pyridine

Product 1

HCID 71572918N-(3-ethynylphenyl)-6-(3-(hexahydrofuro[3,4-c]pyridin-5(3H)-yl)propoxy)-7-methoxyquinazolin-4-amineYield 45.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-((3-ethynylphenyl)amino)-7-methoxyquinazolin-6-ol (250 mg, 0.68 mmol, 1 eq), 5-(3-chloropropyl)octahydrofuro[3,4-c]pyridine (280 mg, 0.82 mmol, 1.2 eq) and K2CO3 (188 mg, 1.36 mmol, 2 eq) in DMF (10 mL) was stirred at 80° C. overnight and cooled to room temperature. To this, CH2Cl2 (50 mL) was added. The mixture was washed with brine (20 mL×3) and water (20 mL×2), then dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by a silica gel column chromatography (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to give the title compound as a yellow solid (140 mg, 45.50%), HPLC: 98.47%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 459.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.73-1.75 (2H, m), 2.35-2.46 (3H, m), 2.54-2.68 (2H, m), 2.65-2.70 (3H, m), 2.72-2.76 (2H, m), 2.96-3.03 (3H, m), 3.05-3.10 (2H, m), 3.71-3.90 (2H, m), 4.03 (1H, s), 4.22-4.27 (2H, m), 7.06-7.12 (1H, m), 7.13 (1H, s), 7.76-7.82 (2H, m), 7.85 (1H, s), 8.06-8.11 (1H, m), 8.55 (1H, s) ppm.

Workup

  1. temperaturecooled to room temperature
  2. washThe mixture was washed with brine (20 mL×3) and water (20 mL×2)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by a silica gel column chromatography (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH)

Sources & evidence

ORD record
ord-c4f89a05b20841ff8652601e591587bf
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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