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5-Tert-butylthiophene-2-carboxylic acid → tert-butyl ((S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl) pyrimidin-2-yl)phenyl)propanoyl)-D-alaninate

HRID 1775853
ノート
印刷プレビュー

反応式

HRID 1775853 の反応式
[NH2:1][C@@H:2]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:30][CH:29]=3)=[CH:24][N:23]=2)=[CH:18][CH:17]=1)[C:3]([NH:5][C@@H:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH3:7])=[O:4].[C:42]([C:46]1[S:50][C:49]([C:51](O)=[O:52])=[CH:48][CH:47]=1)([CH3:45])([CH3:44])[CH3:43].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CC(=O)OCC>[C:42]([C:46]1[S:50][C:49]([C:51]([NH:1][C@@H:2]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[N:27]=[CH:26][C:25]([C:28]4[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:30][CH:29]=4)=[CH:24][N:23]=3)=[CH:18][CH:17]=2)[C:3]([NH:5][C@@H:6]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH3:7])=[O:4])=[O:52])=[CH:48][CH:47]=1)([CH3:45])([CH3:43])[CH3:44]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 4583495-Tert-butylthiophene-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117748653tert-butyl ((S)-2-amino-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)-D-alaninate

生成物 1

HCID 117748654tert-butyl ((S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl) pyrimidin-2-yl)phenyl)propanoyl)-D-alaninate
収率 70.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

Prepared using General Procedure 7. To a stirred solution of tert-butyl ((S)-2-amino-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)-D-alaninate (418 mg, 0.75 mmol), 5-(tert-butyl)thiophene-2-carboxylic acid (137 mg, 0.75 mmol) in DMF (8 mL) was added TEA (208 μl, 1.49 mmol). The mixture was cooled to 0° C. and HATU (298 mg, 0.78 mmol) was added in 2 portions over 5 mins. The mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with EA (150 mL) and washed with saturated aqueous NaHCO3 (100 mL), 1N HCl (100 mL), and brine (100 mL). The organic layer was dried over MgSO4 then concentrated. The crude product was purified by chromatography 0-30% ACN in DCM to afford 382 mg (69%) of tert-butyl ((S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)-D-alaninate as a white solid. LCMS-ESI (m/z) calculated for C42H54N4O5S: 726.4; no m/z observed, tR=3.47 min (Method 11).

後処理

  1. customPrepared
  2. washwashed with saturated aqueous NaHCO3 (100 mL), 1N HCl (100 mL), and brine (100 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationthen concentrated
  5. customThe crude product was purified by chromatography 0-30% ACN in DCM

出典と根拠

ORDレコード
ord-41ef63760d67496982711ebd9c31c7d8
出典データセット
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09260427B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート