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5-Tert-butylthiophene-2-carboxylic acid → (S)-tert-butyl 1-((S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl) propanoyl)pyrrolidine-2-carboxylate

HRID 1775857
ノート
印刷プレビュー

反応式

HRID 1775857 の反応式
[NH2:1][C@@H:2]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[N:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:32][CH:31]=3)=[CH:26][N:25]=2)=[CH:20][CH:19]=1)[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:4].[C:44]([C:48]1[S:52][C:51]([C:53](O)=[O:54])=[CH:50][CH:49]=1)([CH3:47])([CH3:46])[CH3:45].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:44]([C:48]1[S:52][C:51]([C:53]([NH:1][C@@H:2]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[N:29]=[CH:28][C:27]([C:30]4[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:32][CH:31]=4)=[CH:26][N:25]=3)=[CH:20][CH:19]=2)[C:3]([N:5]2[CH2:9][CH2:8][CH2:7][C@H:6]2[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:4])=[O:54])=[CH:50][CH:49]=1)([CH3:47])([CH3:45])[CH3:46]
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 117741043(S)-tert-butyl 1-((S)-2-amino-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)pyrrolidine-2-carboxylate

生成物 1

HCID 117740760
(S)-tert-butyl 1-((S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl) propanoyl)pyrrolidine-2-carboxylate
収率 92.4%

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: A stirred solution of (S)-tert-butyl 1-((S)-2-amino-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)pyrrolidine-2-carboxylate (306 mg, 0.522 mmol) and 5-(tert-butyl)thiophene-2-carboxylic acid (106 mg, 0.574 mmol) in DMF (6 mL) was added TEA (145 μl, 1.043 mmol), cooled to 0° C., then HATU (218 mg, 0.574 mmol) was slowly added over 5 minutes. The reaction was stirred at room temperature for 2 h, then diluted with EA (70 mL), washed with saturated aqueous NaHCO3 (70 mL) and brine (100 mL). The solvent was dried over MgSO4 and removed. The crude product was purified by chromatography 0-30% ACN in DCM to afford 363 mg (92%) of (S)-tert-butyl 1-((S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl) propanoyl)pyrrolidine-2-carboxylate as a sticky solid. LCMS-ESI (m/z) calculated for C44H56N4O5S: 752.4; no m/z observed, tR=11.99 min (Method 10).

後処理

  1. customPrepared
  2. washwashed with saturated aqueous NaHCO3 (70 mL) and brine (100 mL)
  3. dry with materialThe solvent was dried over MgSO4
  4. customremoved
  5. customThe crude product was purified by chromatography 0-30% ACN in DCM

出典と根拠

ORDレコード
ord-d68a9bf9145b4868be90bf2b4130d6fa
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…

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