[((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 1864351ノート

反応式

HRID 1864351 の反応式
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

参加物

3

反応物 1

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

実験手順

[((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.

後処理

  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

出典と根拠

ORDレコード
ord-48431c9dad3642c5bd0d9e578c606cb2
出典データセット
uspto-grants-2009_12
特許番号
US07625908B2

反応ノート

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