Diisopropylethylamine → 1-[2-(S)-amino-3-thiophen-2-yl-propionyl]-4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid cyclohexylmethylamide

HRID 2360966ノート

反応式

HRID 2360966 の反応式
[CH:1]1([CH2:7][NH:8][C:9]([C:11]2([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:20][CH:19]=3)[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(OC([NH:37][C@@H:38]([CH2:42][C:43]1[S:44][CH:45]=[CH:46][CH:47]=1)[C:39](O)=[O:40])=O)(C)(C)C.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:1]1([CH2:7][NH:8][C:9]([C:11]2([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)=[CH:22][CH:23]=3)[CH2:16][CH2:15][N:14]([C:39](=[O:40])[C@@H:38]([NH2:37])[CH2:42][C:43]3[S:44][CH:45]=[CH:46][CH:47]=3)[CH2:13][CH2:12]2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27344843-(Thien-2-yl)-L-alanine, N-BOC protectedHCID 673848954-Biphenyl-4-ylmethyl-piperidine-4-carboxylic acid cyclohexylmethylamide

生成物 1

HCID 533788601-[2-(S)-amino-3-thiophen-2-yl-propionyl]-4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid cyclohexylmethylamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid cyclohexylmethylamide (3.98 mmol; 1.7 g) in DMF (20 mL) was added (S)-2-tert-butoxycarbonylamino-3-thiophen-2-yl-propionic acid (4.63 mmol; 1.26 g), N,N-diisopropyl-N-ethylamine (13.9 mmol; 2.46 mL) and HBTU (6.02 mmol; 2.28 g), and the resulting mixture was stirred at room temperature overnight. The resulting mixture was then purified via reverse phase HPLC and the desired fractions were combined and lyophilized. The residue was dissolved in THF (5 mL) and a 4N HCl solution in 1,4-dioxane (15 mL) was added. The resulting solution was stirred for 7 hours at room temperature and evaporated. The residue was triturated with diethyl ether and dried under vacuum to yield 1-[2-(S)-amino-3-thiophen-2-yl-propionyl]-4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid cyclohexylmethylamide as a hydrochloride salt.

後処理

  1. customThe resulting mixture was then purified via reverse phase HPLC
  2. dissolutionThe residue was dissolved in THF (5 mL)
  3. additiona 4N HCl solution in 1,4-dioxane (15 mL) was added
  4. stirringThe resulting solution was stirred for 7 hours at room temperature
  5. customevaporated
  6. customThe residue was triturated with diethyl ether
  7. customdried under vacuum

出典と根拠

ORDレコード
ord-7fb86c01118b4d35977ba3d41417241a
出典データセット
uspto-grants-2014_04
特許番号
US08686152B2

反応ノート

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