Phenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamate → 1-(3-(2-Fluoropropan-2-yl)isoxazol-5-yl)-3-(3-(6-methoxy-7-(2-morpholinoethoxy)quinazolin-4-yloxy)phenyl)urea

HRID 871616Notes

Reaction equation

HRID 871616 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)[N:9]=[CH:8][N:7]=[C:6]2[O:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][CH:29]=1)[NH2:26].[F:30][C:31]([C:34]1[CH:38]=[C:37]([NH:39][C:40](=O)[O:41]C2C=CC=CC=2)[O:36][N:35]=1)([CH3:33])[CH3:32]>CN(C)C1C=CN=CC=1>[F:30][C:31]([C:34]1[CH:38]=[C:37]([NH:39][C:40]([NH:26][C:25]2[CH:27]=[CH:28][CH:29]=[C:23]([O:22][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][N:16]5[CH2:21][CH2:20][O:19][CH2:18][CH2:17]5)=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)[CH:24]=2)=[O:41])[O:36][N:35]=1)([CH3:32])[CH3:33]

Participants

4

Reactant 2

HCID 66876626Phenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamateHCID 668766313-(6-Methoxy-7-(2-morpholinoethoxy)quinazolin-4-yloxy)aniline

Product 1

HCID 582677631-(3-(2-Fluoropropan-2-yl)isoxazol-5-yl)-3-(3-(6-methoxy-7-(2-morpholinoethoxy)quinazolin-4-yloxy)phenyl)ureaYield 49%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

Using the procedure described in Example 229B by using 3-(6-methoxy-7-(2-morpholinoethoxy)quinazolin-4-yloxy)aniline described in Example 251A Step 3 (146 mg, 0.37 mmol) was reacted with phenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamate from Example 42A (117 mg, 0.44 mmol) and 4-(dimethylamino)pyridine (45 mg, 0.37 mmol) to give 1-(3-(2-fluoropropan-2-yl)isoxazol-5-yl)-3-(3-(6-methoxy-7-(2-morpholinoethoxy)quinazolin-4-yloxy)phenyl)urea (101.6 mg, 49%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 10.41 (s, 1H), 9.11 (s, 1H), 8.56 (s, 1H), 7.57 (s, 2H), 7.44-7.40 (m, 2H), 7.32 (d, 1H), 7.00 (d, 1H), 6.15 (s, 1H), 4.35-4.33 (m, 2H), 3.98 (s, 3H), 3.62-3.60 (m, 4H), 2.85-2.70 (m, 2H), 2.52-2.50 (m, 4H), 1.70 (s, 3H), 1.63 (s, 3H); LC-MS (ESI) m/z 567 (M+H)+.

Sources & evidence

ORD record
ord-12396569fa4941c39573c3266788641c
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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