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

HRID 1864350ノート

反応式

HRID 1864350 の反応式
[NH2:1][CH2:2][C@@H:3]([CH3:31])[O:4][C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[C:7]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[C:18]([Cl:30])[CH:17]=1)=[N:8][CH:9]=[N:10]2.CCN(C(C)C)C(C)C.[C:41]([O:45][C:46]([N:48]([CH2:50][C:51](O)=[O:52])[CH3:49])=[O:47])([CH3:44])([CH3:43])[CH3:42].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:41]([O:45][C:46](=[O:47])[N:48]([CH2:50][C:51](=[O:52])[NH:1][CH2:2][C@H:3]([O:4][C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[C:7]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[C:18]([Cl:30])[CH:17]=1)=[N:8][CH:9]=[N:10]2)[CH3:31])[CH3:49])([CH3:44])([CH3:42])[CH3:43]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 83692Glycine, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 690596285-[(1R)-2-amino-1-methylethoxy]-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]quinazolin-4-amine

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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, 868 mg) was stirred in DCM (40 ml) with DIPEA (1 ml). N-(tert-butoxycarbonyl)sarcosine (400 mg) and HATU (800 mg) were added and mixture was stirred for 18 hours. Volatile material was removed by evaporation and the residue was purified by chromatography, eluting with increasing concentrations of methanol in ethyl acetate (0-10%). Evaporation of the appropriate fractions gave the title compound as a froth (0.50 g); NMR spectrum (DMSO-d6 @ 373k) 1.10 (s, 6H), 1.20 (s, 3H), 1.40-1.42 (d, 3H), 2.72 (s, 3H), 3.40-3.60 (d, 1H, (masked by H2O), 3.60-3.75 (q, 2H), 3.75-3.80 (d, 1H), 4.90-5.00 (bs, 1H), 5.30 (s, 2H), 7.28-7.34 (q, 2H), 7.34-7.40 (m, 1H), 7.42-7.46 (d, 1H), 7.50-7.62 (m, 2H), 7.85-7.91 (dt, 1H), 7.91-7.99 (m, 2H), 8.24-8.34 (bs, 1H), 8.57-8.62 (d, 1H), 8.75 (s, 1H), 10.60-10.70 (bs, 1H); Mass spectrum MH+ 607.

後処理

  1. customVolatile material was removed by evaporation
  2. customthe residue was purified by chromatography
  3. washeluting
  4. temperaturewith increasing concentrations of methanol in ethyl acetate (0-10%)
  5. customEvaporation of the appropriate fractions

出典と根拠

ORDレコード
ord-4779d0b3ba754bbbaab30538275dcefa
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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