[((R)-2-{4-[3-Chloro-4-(pyridin-2-ylmethoxy)phenylamino]quinazolin-5-yloxy}propylcarbamoyl)methyl]methylcarbamic acid tert-butyl ester → N1-{(2R)-2-[(4-{[3-Chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}quinazolin-5-yl)oxy]propyl}-N2-methylglycinamide

HRID 1864351Notes

Reaction equation

HRID 1864351 reaction equation
C(O[C:6](=O)[N:7]([CH2:9][C:10](=[O:42])[NH:11][CH2:12][C@H:13]([O:15][C:16]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:17]=1[C:18]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)=[C:29]([Cl:41])[CH:28]=1)=[N:19][CH:20]=[N:21]2)[CH3:14])C)(C)(C)C>FC(F)(F)C(O)=O>[Cl:41][C:29]1[CH:28]=[C:27]([NH:26][C:18]2[C:17]3[C:22](=[CH:23][CH:24]=[CH:25][C:16]=3[O:15][C@H:13]([CH3:14])[CH2:12][NH:11][C:10](=[O:42])[CH2:9][NH:7][CH3:6])[N:21]=[CH:20][N:19]=2)[CH:32]=[CH:31][C:30]=1[O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1

Participants

3

Reactant 1

HCID 57974348[((R)-2-{4-[3-Chloro-4-(pyridin-2-ylmethoxy)phenylamino]quinazolin-5-yloxy}propylcarbamoyl)methyl]methylcarbamic acid tert-butyl ester

Product 1

HCID 57974349N1-{(2R)-2-[(4-{[3-Chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}quinazolin-5-yl)oxy]propyl}-N2-methylglycinamideYield 15%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

[((R)-2-{4-[3-Chloro-4-(pyridin-2-ylmethoxy)phenylamino]quinazolin-5-yloxy}propylcarbamoyl)methyl]methylcarbamic acid tert-butyl ester (obtained as described in Example 123, 0.50 g) was stirred in trifluoroacetic acid (5 ml) for 20 hours. Volatile material was removed by evaporation and the residue was purified by chromatography, eluting with aqueous ammonia (0.880), methanol, DCM (1:10:90). Evaporation of the appropriate fractions gave the title compound as a solid (60 mg, 15%); (DMSO-d6 @ 373k) 1.47-1.50 (d, 3H), 2.20 (s, 3H), 3.10 (s, 2H), 3.45-3.55 (q, 1H), 3.55-3.65 (q, 1H), 4.85-5.00 (m, 1H), 5.25 (s, 2H), 7.15-7.25 (q, 2H), 7.25-7.30 (m, 2H), 7.55-7.65 (t, 1H), 7.70-7.80 (m, 2H), 8.20 (s, 1H), 8.50 (s, 1H), 8.55-8.60 (d, 1H), 9.85-9.95 (bs, 1H); Mass spectrum MH+ 507.

Workup

  1. customVolatile material was removed by evaporation
  2. customthe residue was purified by chromatography
  3. washeluting with aqueous ammonia (0.880), methanol, DCM (1:10:90)
  4. customEvaporation of the appropriate fractions

Sources & evidence

ORD record
ord-48431c9dad3642c5bd0d9e578c606cb2
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

Loading…