4-(Chloromethyl)-1,3-thiazole → 2-Hydroxy-N-methyl-N-{(2R)-2-[(4-{[3-methyl-4-(1,3-thiazol-4-ylmethoxy)phenyl]amino}quinazolin-5-yl)oxy]propyl}acetamide

HRID 1864315Notes

Reaction equation

HRID 1864315 reaction equation
Cl[CH2:2][C:3]1[N:4]=[CH:5][S:6][CH:7]=1.[OH:8][CH2:9][C:10]([N:12]([CH2:14][C@H:15]([O:17][C:18]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:19]=1[C:20]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[C:31]([CH3:36])[CH:30]=1)=[N:21][CH:22]=[N:23]2)[CH3:16])[CH3:13])=[O:11]>>[OH:8][CH2:9][C:10]([N:12]([CH3:13])[CH2:14][C@H:15]([O:17][C:18]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:19]=1[C:20]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:2][C:3]3[N:4]=[CH:5][S:6][CH:7]=3)=[C:31]([CH3:36])[CH:30]=1)=[N:21][CH:22]=[N:23]2)[CH3:16])=[O:11]

Participants

3

Reactant 2

HCID 27632904-(Chloromethyl)-1,3-thiazoleHCID 690577712-hydroxy-N-[(2R)-2-({4-[(4-hydroxy-3-methylphenyl)amino]quinazolin-5-yl}oxy)propyl]-N-methylacetamide

Product 1

HCID 579743452-Hydroxy-N-methyl-N-{(2R)-2-[(4-{[3-methyl-4-(1,3-thiazol-4-ylmethoxy)phenyl]amino}quinazolin-5-yl)oxy]propyl}acetamideYield 41%

Procedure

The procedure described in Example 3 was repeated using 4-(chloromethyl)-1,3-thiazole and 2-hydroxy-N-[(2R)-2-({4-[(4-hydroxy-3-methylphenyl)amino]quinazolin-5-yl}oxy)propyl]-N-methylacetamide (obtained as described in Example 90, preparation of starting materials) to give the title compound as a white solid in 41% yield; NMR spectrum (DMSO-d6 373K) 1.43 (d, 3H), 2.24 (s, 3H), 2.97 (s, 3H), 3.57 (m, 1H), 4.07 (m, 3H), 5.13 (m, 1H), 5.25 (s, 2H), 7.09 (d, 1H), 7.11 (d, 1H), 7.34 (d, 1H), 7.57 (m, 2H), 7.69 (m, 2H), 8.42 (s, 1H), 9.07 (d, 1H), 9.82 (s, 1H); Mass spectrum MH+ 494.

Sources & evidence

ORD record
ord-e1feae0fc61143488a7704ff40f0a389
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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