Cyclohexanone → 8'-fluoro-5'-methoxy-1'H-spiro[cyclohexane-1,4'-quinazolin]-2'(3'H)-one

HRID 33408Notes

Reaction equation

HRID 33408 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[NH:10][C:11]([NH2:13])=[O:12].[C:14]1(=O)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]2[C:3]=1[NH:10][C:11](=[O:12])[NH:13][C:14]12[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

3

Reactant 2

HCID 7967CyclohexanoneHCID 22931854N-(2-Fluoro-5-methoxyphenyl)urea

Product 1

HCID 693174648'-fluoro-5'-methoxy-1'H-spiro[cyclohexane-1,4'-quinazolin]-2'(3'H)-oneYield 70%

Conditions

Temperature
100 °C

Procedure

To a stirred solution of polyphosphoric acid (20 g) at 100° C. was added N-(2-fluoro-5-methoxyphenyl)urea (900 mg, 4.89 mmol) over 5 minutes followed by cyclohexanone (719 mg, 7.33 mmol) in one portion under N2. The mixture was stirred at 100° C. for 2 hours, cooled to 35° C. and quenched into water (400 mL). The crude product was filtered and washed with water (100 mL). The isolated solid was slurred in a mixture of tert-butylmethylether (8 mL) and ethyl acetate (4 mL) at 50° C. for 10 minutes, filtered, washed with tert-butylmethylether (10 mL) and dried in vacuo at 40° C. to give 8′-fluoro-5′-methoxy-1′H-spiro[cyclohexane-1,4′-quinazolin]-2′(3′H)-one (900 mg, 70%) as a light-brown solid, purity (97.3%).

Workup

  1. temperaturecooled to 35° C.
  2. customquenched into water (400 mL)
  3. filtrationThe crude product was filtered
  4. washwashed with water (100 mL)
  5. additionThe isolated solid was slurred in a mixture of tert-butylmethylether (8 mL) and ethyl acetate (4 mL) at 50° C. for 10 minutes
  6. filtrationfiltered
  7. washwashed with tert-butylmethylether (10 mL)
  8. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-6f428cf05d084d26b1b6eaf06aed9c68
Source dataset
uspto-grants-2008_09
Patent number
US07429598B2

Reaction notes

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