Carbamate → HCID 44243438, compound

HRID 1917856Notes

Reaction equation

HRID 1917856 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].[C:23](=O)([O-])[NH2:24].COC1C=C2C(=CC=1OC)N=CN=C2OC1C=C(N[C:49]([NH:51][C:52]2[O:56][N:55]=[C:54]([CH:57]([CH3:59])[CH3:58])[CH:53]=2)=[O:50])C=CC=1>>[C:23]([C:57]([C:54]1[CH:53]=[C:52]([NH:51][C:49]([NH:19][C:18]2[CH:20]=[CH:21][CH:22]=[C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)[CH:17]=2)=[O:50])[O:56][N:55]=1)([CH3:58])[CH3:59])#[N:24]

Participants

4

Reactant 3

HCID 276CarbamateHCID 442434351-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropylisoxazol-5-yl)ureaHCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline

Product 1

HCID 44243438HCID 44243438, compoundYield 39%

Procedure

Prepared from 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline from Example 113A (89 mg, 0.30 mmol) and the carbamate from the previous step (90 mg, 0.332 mmol) according to the method described for 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropylisoxazol-5-yl)urea in Example 122B, except the reaction mixture was stirred at room temperature for 3 h. Purification via silica gel chromatography eluting with 100% dichloromethane to 10% methanol in dichloromethane afforded 1-(3-(2-cyanopropan-2-yl)isoxazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea as a colorless solid (55 mg, 39%). 1H NMR (300 MHz, DMSO-d6) δ 10.51 (brs, 1H), 9.12 (brs, 1H), 8.57 (s, 1H), 7.56-7.57 (m, 2H), 7.31-7.45 (m, 3H), 7.01 (m, 1H), 6.27 (s, 1H), 4.00 (s, 6H), 1.68 (s, 6H); LC-MS (ESI) m/z 475 (M+H)+.

Workup

  1. customPurification via silica gel chromatography
  2. washeluting with 100% dichloromethane to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-ae7819bb2cb642178b2789270ab2efac
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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