[((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 1864351노트

반응식

HRID 1864351 반응식
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

참가 물질

3

반응물 1

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

생성물 1

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

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

실험 절차

[((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.

후처리

  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

출처 및 근거

ORD 기록
ord-48431c9dad3642c5bd0d9e578c606cb2
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07625908B2

반응 노트

불러오는 중…