Trifluoroacetic acid → HCID 136337770, compound

HRID 871333Notes

Reaction equation

HRID 871333 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[CH:21]=[C:22]([NH:26][C:27]([NH:29][C:30]4[CH:34]=[C:33]([C:35]([CH3:38])([CH3:37])[CH3:36])[O:32][N:31]=4)=[O:28])[CH:23]=[CH:24][CH:25]=3)=[N:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1)C1C=CC=CC=1.FC(F)(F)C(O)=O>>[C:35]([C:33]1[O:32][N:31]=[C:30]([NH:29][C:27]([NH:26][C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([O:19][C:13]3[C:12]4[C:17](=[CH:18][C:9]([OH:8])=[CH:10][CH:11]=4)[N:16]=[CH:15][N:14]=3)[CH:21]=2)=[O:28])[CH:34]=1)([CH3:38])([CH3:36])[CH3:37]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66876450HCID 66876450, compound

Product 1

HCID 136337770HCID 136337770, compoundYield 60.1%

Conditions

Temperature
85 °C

Procedure

1-(3-(7-(Benzyloxy)quinazolin-4-yloxy)phenyl)-3-(5-tert-butylisoxazol-3-yl)urea (725 mg, 1.42 mmol) was treated with trifluoroacetic acid (7 mL) and heated at 85° C. for 3 h. The solvent was removed under reduced pressure and the residue dissolved in ethyl acetate/water. The solution was neutralized with saturated sodium bicarbonate (pH=8) and the organic layer separated. After extraction of the aqueous phase with ethyl acetate, the organic fractions were combined, dried (MgSO4) and concentrated under reduced pressure. The solid was triturated with ethyl acetate to afford 1-(5-tert-butylisoxazol-3-yl)-3-(3-(7-hydroxyquinazolin-4-yloxy)phenyl)urea (358 mg, 60%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 10.92 (s, 1H), 9.64 (s, 1H), 9.07 (s, 1H), 8.58 (s, 1H), 8.24 (d, 1H), 7.57 (s, 1H), 7.41 (t, 1H), 7.30 (d, 2H), 7.20 (s, 1H), 6.97 (d, 1H) 6.49 (s, 1H), 1.27 (s, 9H); LC-MS (ESI) m/z 420 (M+H)+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue dissolved in ethyl acetate/water
  3. customthe organic layer separated
  4. extractionAfter extraction of the aqueous phase with ethyl acetate
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe solid was triturated with ethyl acetate

Sources & evidence

ORD record
ord-cef3d8fdebcd4299b0137de076eaf13d
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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