tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylate → (R)-tert-butyl 3-(4-(3-(3-(5-tert-butylisoxazol-3-yl)ureido)phenoxy)-6-methoxyquinazolin-7-yloxy)pyrrolidine-1-carboxylate

HRID 871404Notes

Reaction equation

HRID 871404 reaction equation
C(C1ON=C(NC(NC2C=CC=C(OC3C4C(=CC(O)=C(OC)C=4)N=CN=3)C=2)=O)C=1)(C)(C)C.O[C@H]1CCN(C(OC(C)(C)C)=O)C1.[C:47]([C:51]1[O:55][N:54]=[C:53]([NH:56][C:57](=[O:91])[NH:58][C:59]2[CH:60]=[C:61]([CH:88]=[CH:89][CH:90]=2)[O:62][C:63]2[C:72]3[C:67](=[CH:68][C:69]([O:75][C@H:76]4[CH2:80][CH2:79][N:78]([C:81]([O:83][C:84]([CH3:87])([CH3:86])[CH3:85])=[O:82])[CH2:77]4)=[C:70]([O:73][CH3:74])[CH:71]=3)[N:66]=[CH:65][N:64]=2)[CH:52]=1)([CH3:50])([CH3:49])[CH3:48]>>[C:47]([C:51]1[O:55][N:54]=[C:53]([NH:56][C:57](=[O:91])[NH:58][C:59]2[CH:60]=[C:61]([CH:88]=[CH:89][CH:90]=2)[O:62][C:63]2[C:72]3[C:67](=[CH:68][C:69]([O:75][C@@H:76]4[CH2:80][CH2:79][N:78]([C:81]([O:83][C:84]([CH3:86])([CH3:85])[CH3:87])=[O:82])[CH2:77]4)=[C:70]([O:73][CH3:74])[CH:71]=3)[N:66]=[CH:65][N:64]=2)[CH:52]=1)([CH3:48])([CH3:49])[CH3:50]

Participants

4

Reactant 3

HCID 854055tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylateHCID 66876528(S)-tert-butyl 3-(4-(3-(3-(5-tert-butylisoxazol-3-yl)ureido)phenoxy)-6-methoxyquinazolin-7-yloxy)pyrrolidine-1-carboxylateHCID 1360737521-(5-Tert-butylisoxazol-3-yl)-3-(3-(7-hydroxy-6-methoxyquinazolin-4-yloxy)phenyl)urea

Product 1

HCID 66877259(R)-tert-butyl 3-(4-(3-(3-(5-tert-butylisoxazol-3-yl)ureido)phenoxy)-6-methoxyquinazolin-7-yloxy)pyrrolidine-1-carboxylateYield 23%

Procedure

Prepared from 1-(5-tert-butylisoxazol-3-yl)-3-(3-(7-hydroxy-6-methoxyquinazolin-4-yloxy)phenyl)urea from Example 95B (350 mg, 0.780 mmol) and (S)-3-hydroxy-1-tert-butoxycarbonylpyrrolidine (219 mg, 1.17 mmol) according to the procedure described for (S)-tert-butyl 3-(4-(3-(3-(5-tert-butylisoxazol-3-yl)ureido)phenoxy)-6-methoxyquinazolin-7-yloxy)pyrrolidine-1-carboxylate in Example 96A to afford (R)-tert-butyl 3-(4-(3-(3-(5-tert-butylisoxazol-3-yl)ureido)phenoxy)-6-methoxyquinazolin-7-yloxy)pyrrolidine-1-carboxylate as a colorless oil (109 mg, 23%). 1H NMR (300 MHz, DMSO-d6) δ 9.58 (brs, 1H), 9.00 (brs, 1H), 8.57 (s, 1H), 7.50-7.70 (m, 2H), 7.40-7.50 (m, 2H), 7.30 (m, 1H), 7.00 (m, 1H), 6.48 (s, 1H), 5.30 (brs, 1H), 4.00 (s, 3H), 3.70 (m, 1H), 3.40-3.50 (m, 2H), 3.25 (m, 1H), 2.20-2.40 (m, 2H), 1.40 (s, 9H), 1.30 (s, 9H); LC-MS (ESI) m/z 619 (M+H)+.

Sources & evidence

ORD record
ord-846aee95341c4652aa029a2c0ada5683
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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