Hydrochloric Acid → (S)-1-(5-tert-butylisoxazol-3-yl)-3-{3-[6-methoxy-7-(pyrrolidin-3-yloxy)quinazolin-4-yloxy]phenyl}urea

HRID 631367Notes

Reaction equation

HRID 631367 reaction equation
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11](=[O:45])[NH:12][C:13]2[CH:14]=[C:15]([CH:42]=[CH:43][CH:44]=2)[O:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:29][C@H:30]4[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31]4)=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl>C(Cl)Cl.O1CCOCC1>[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:12][C:13]2[CH:44]=[CH:43][CH:42]=[C:15]([O:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:29][C@H:30]5[CH2:34][CH2:33][NH:32][CH2:31]5)=[C:24]([O:27][CH3:28])[CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH:14]=2)=[O:45])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 66876528(S)-tert-butyl 3-(4-(3-(3-(5-tert-butylisoxazol-3-yl)ureido)phenoxy)-6-methoxyquinazolin-7-yloxy)pyrrolidine-1-carboxylate

Product 1

HCID 58267880(S)-1-(5-tert-butylisoxazol-3-yl)-3-{3-[6-methoxy-7-(pyrrolidin-3-yloxy)quinazolin-4-yloxy]phenyl}ureaYield 77.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-tert-butyl 3-(4-{3-[3-(5-tert-butylisoxazol-3-yl)ureido]phenoxy}-6-methoxyquinazolin-7-yloxy)pyrrolidine-1-carboxylate (0.609 g, 0.98 mmol) in CH2Cl2 (10 mL) was dropped 4.0 M solution of HCl in 1,4-dioxane (2 mL) and it was stirred at room temperature for 4 hours. After solvents were concentrated under reduced pressure, it was dissolved in CH2Cl2 with a few milliliters of MeOH and washed with saturated NaHCO3 solution. The organic layer was dried over MgSO4 and concentrated to dryness under reduced pressure to afford (S)-1-(5-tert-butylisoxazol-3-yl)-3-{3-[6-methoxy-7-(pyrrolidin-3-yloxy)quinazolin-4-yloxy]phenyl}urea as a white solid (0.396 g, 77%). 1H NMR (300 MHz, CDCl3) δ 9.4 (s, 1H), 8.61 (s, 1H), 8.5 (s, 1H), 7.67 (m, 2H), 7.49 (m, 2H), 7.38 (t, 1H), 6.99 (d, 1H), 5.99 (s, 1H), 5.05 (m, 1H), 4.01 (s, 3H), 3.40 (m, 1H), 3.21 (m, 2H), 3.0 (m, 1H), 2.3 (m, 1H), 2.1 (m, 2H), 1.32 (s, 9H); LC-MS (ESI) m/z 519 (M+H)+.

Workup

  1. concentrationAfter solvents were concentrated under reduced pressure, it
  2. dissolutionwas dissolved in CH2Cl2 with a few milliliters of MeOH
  3. washwashed with saturated NaHCO3 solution
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-8434e21b6ec84d55868586fda1791e89
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

Loading…