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

HRID 871403Notes

Reaction equation

HRID 871403 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].[ClH:46]>O1CCOCC1.ClCCl>[ClH:46].[ClH:46].[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 66876708(S)-1-(5-tert-butylisoxazol-3-yl)-3-(3-(6-methoxy-7-(pyrrolidin-3-yloxy)quinazolin-4-yloxy)phenyl)urea dihydrochlorideYield 67%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (S)-tert-butyl 3-(4-(3-(3-(5-tert-butylisoxazol-3-yl)ureido)phenoxy)-6-methoxyquinazolin-7-yloxy)pyrrolidine-1-carboxylate from the previous step (35 mg, 0.0566 mmol) and hydrochloric acid (0.1 mL of a 4N solution in 1,4-dioxane, 0.40 mmol) in dry dichloromethane (0.01 mL) was stirred at room temperature for 2 h. Concentrated 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 dihydrochloride as a colorless solid (22 mg, 67%), which did not require further purification. 1H NMR (300 MHz, MeOH-d4) δ 9.02 (brs, 1H), 7.82 (s, 1H), 7.73 (brs, 1H), 7.54 (s, 1H), 7.41 (m, 1H), 7.29 (m, 1H), 7.06 (m, 1H), 6.32 (s, 1H) 5.56 (brs, 1H), 4.04 (s, 3H), 3.50-3.85 (m, 5H), 2.50-2.60 (m, 2H), 1.35 (s, 9H); LC-MS (ESI) m/z 519 (M+H)+.

Workup

  1. concentrationConcentrated under reduced pressure

Sources & evidence

ORD record
ord-53e882a32bd44a59a334bebd16996572
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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