Potassium Carbonate → HCID 53630902, compound

HRID 2102436Notes

Reaction equation

HRID 2102436 reaction equation
Cl.[Cl:2][C:3]1[C:4]([F:24])=[C:5]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([OH:23])=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:6]=[CH:7][C:8]=1[Cl:9].C(=O)([O-])[O-].[K+].[K+].CS(O[CH2:36][CH:37]1[CH2:46][N:45]2[CH:40]([CH2:41][CH2:42][CH2:43][CH2:44]2)[CH2:39][CH2:38]1)(=O)=O>CN(C)C=O>[Cl:2][C:3]1[C:4]([F:24])=[C:5]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:23][CH2:36][CH:37]4[CH2:46][N:45]5[CH:40]([CH2:41][CH2:42][CH2:43][CH2:44]5)[CH2:39][CH2:38]4)=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:6]=[CH:7][C:8]=1[Cl:9]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86604088HCID 86604088, compoundHCID 136335144HCID 136335144, compound

Product 1

HCID 53630902HCID 53630902, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

4-[(3,4-Dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-ol hydrochloride (469 mg, 1.20 mmol) was dissolved in dimethylformamide (1 mL) and potassium carbonate (828 mg, 6.00 mmol) was added followed by octahydro-2H-quinolizin-3-ylmethyl methanesulfonate (466 mg, 1.89 mmol) in dimethylformamide (1 mL). The mixture was stirred at 70° C. for 38 h and then was partitioned between ethyl acetate and water. The aqueous portion was extracted with ethyl acetate. The combined organic portion was dried over sodium sulfate, filtered and concentrated in vacuo to afford a brown oil which was purified by column chromatography (15-20% methanol in dichloromethane). The purified material was crystallized from methanol to afford N-(3,4-dichloro-2-fluorophenyl)-6-(methyloxy)-7-[(octahydro-2H-quinolizin-3-ylmethyl)oxy]quinazolin-4-amine as a cream colored solid (83.4 mg, 0.165 mmol, 14% yield). 1H NMR (400 MHz, CDCl3): 8.69 (s, 1H), 8.53 (t, 1H), 7.34 (dd, 1H), 7.28-7.22 (m, 1H), 7.23 (s, 1H), 6.98 (s, 1H), 4.06-3.95 (m, 2H), 4.02 (s, 3H), 3.09 (d, 1H), 2.87 (d, 1H), 2.43-2.27 (m, 1H), 2.10-1.97 (m, 1H), 1.95-1.84 (m, 2H), 1.80-1.52 (m, 5H), 1.46-0.95 (m, 5H); MS (EI) for C25H27N4O2FCl2: 505 (MH+).

Workup

  1. customwas partitioned between ethyl acetate and water
  2. extractionThe aqueous portion was extracted with ethyl acetate
  3. dry with materialThe combined organic portion was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford a brown oil which
  7. customwas purified by column chromatography (15-20% methanol in dichloromethane)
  8. customThe purified material was crystallized from methanol

Sources & evidence

ORD record
ord-39b2cc78d0df4af7a43abe3726fd05b9
Source dataset
uspto-grants-2009_08
Patent number
US07576074B2

Reaction notes

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