Methyl Isocyanate → N-{(2R)-2-[(4-{[3-Chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}quinazolin-5-yl)oxy]propyl}-N'-methylurea

HRID 1864349Notes

Reaction equation

HRID 1864349 reaction equation
[CH3:1][N:2]=[C:3]=[O:4].[NH2:5][CH2:6][C@@H:7]([CH3:35])[O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[C:11]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[C:22]([Cl:34])[CH:21]=1)=[N:12][CH:13]=[N:14]2>>[Cl:34][C:22]1[CH:21]=[C:20]([NH:19][C:11]2[C:10]3[C:15](=[CH:16][CH:17]=[CH:18][C:9]=3[O:8][C@H:7]([CH3:35])[CH2:6][NH:5][C:3]([NH:2][CH3:1])=[O:4])[N:14]=[CH:13][N:12]=2)[CH:25]=[CH:24][C:23]=1[O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1

Participants

3

Reactant 2

HCID 12228Methyl IsocyanateHCID 690596285-[(1R)-2-amino-1-methylethoxy]-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]quinazolin-4-amine

Product 1

HCID 57974280N-{(2R)-2-[(4-{[3-Chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}quinazolin-5-yl)oxy]propyl}-N'-methylureaYield 43%

Procedure

The procedure described in Example 120 was repeated using methyl isocyanate and 5-[(1R)-2-amino-1-methylethoxy]-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]quinazolin-4-amine (obtained as described in Example 65, preparation of starting materials) to give the title compound as a solid in 43% yield; NMR spectrum (DMSO-d6 @ 373K) 1.40-1.45 (d, 3H), 2.50-2.55 (d, 3H), 3.38-3.48 (m, 1H), 3.50-3.60 (m, 1H), 4.83-4.92 (m, 1H), 5.28 (s, 2H), 5.55-5.65 (bs, 1H), 6.00-6.10 (bs, 1H), 7.19-7.24 (dd, 2H), 7.31-7.37 (m, 2H), 7.56-7.62 (m, 2H), 7.66-7.73 (t, 1H), 7.81-7.88 (dt, 1H), 8.06-8.08 (d, 1H), 8.48 (s, 1H), 8.55-8.60 (d, 1H), 9.95-10.05 (bs, 1H); Mass spectrum MH+ 493.4.

Sources & evidence

ORD record
ord-3835b2e0dd114f9e9ce6d7118d137c50
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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