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4-Methylmorpholine → 2-{4-[2-Tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-ethyl-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methyl ester

HRID 720178
ノート
印刷プレビュー

反応式

HRID 720178 の反応式
[CH3:1][O:2][C:3](=[O:24])[CH:4]([N:16]1[CH2:21][CH2:20][NH:19][CH:18]([CH2:22][CH3:23])[CH2:17]1)[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.[CH3:25][C:26]([O:29][C:30]([NH:32][C@@H:33]([C:42](O)=[O:43])[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=1)=[O:31])([CH3:28])[CH3:27].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.O.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:24])[CH:4]([N:16]1[CH2:21][CH2:20][N:19]([C:42](=[O:43])[CH:33]([NH:32][C:30]([O:29][C:26]([CH3:27])([CH3:25])[CH3:28])=[O:31])[CH2:34][C:35]2[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=2)[CH:18]([CH2:22][CH3:23])[CH2:17]1)[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1
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

8

反応物 4

HCID 79724-MethylmorpholineHCID 2734493(2R)-2-(((tert-butoxy)carbonyl)amino)-3-(4-fluorophenyl)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 695875432-(3-Ethyl-piperazin-1-yl)-3-naphthalen-2-yl-propionic acid methyl ester

生成物 1

HCID 69587568
2-{4-[2-Tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-ethyl-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methyl ester
収率 91%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

2-(3-Ethyl-piperazin-1-yl)-3-naphthalen-2-yl-propionic acid methyl ester, 34, (2.1 g, 6.4 mmol) and N-Boc-D-4-fluorophenylalanine (1.9 g, 6.8 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (4.9 g, 12.9 mmol) are dissolved in anhydrous DMF (20 mL). This reaction mixture is cooled to 0° C., then N-methylmorpholine (0.75 mL, 6.8 mmol) is added. The reaction mixture is placed in a refrigerator overnight. EtOAc (75 mL) and water (300 mL) are added, and the organic layer is separated. The aqueous layer is extracted with EtOAc (3×150 mL). The combined organic layers are washed with water (100 mL), dried over Na2SO4, and concentrated in vacuo. The resulting residue is purified over silica (EtOAc/Hexane, 1:2) to afford 3.5 g (91% yield) of the desired product. 1H NMR (CDCl3, δ): 7.82–7.75 (m, 3H), 7.62 (s, 1H), 7.52–7.40 (M, 2H), 7.34 (m, 1H), 7.22–7.25 (m, 2H), 7.02–6.92 (m2H), 5.75–5.62 (M, 1H), 5.18 (d, J=7.7 Hz, 0.5H), 4.90 (quartet, J=7.7 Hz, 1H), 4750–4.62 (m, 0.5H), 4.50–4.25 (m, 1H), 3.64 (d, J=9.7 Hz, 3H), 3.58–3.38 (m, 1.5H), 3.30–2.90 (m, 6H), 2.90–2.70 (m, 1H), 2.62–2.25 (d, J=11.6 Hz, 1H), 2.15–2.00 (m, 1H), 1.78–1.50 (m, 1.5H), 1.42 (s, 9H), 1.35–1.20 (m, 1H), 0.6 (t, J=9.7 Hz, 2H); 13C NMR, δ 174.2, 171.6, 171.0, 170.2, 164.0, 160.2, 156, 135.7, 133.7, 132.4, 131.4, 131.3, 128.1, 127.8, 127.6, 127.5, 126.2, 125.7, 115.7, 115.5, 115.4, 115.3, 79.9, 68.9, 68.7, 55.9, 54.1, 53.7, 51.4, 51.2, 51.0, 47.5, 46.6, 40.1, 39.1, 38.1, 35.4, 28.5, 22.9, 21.9, 10.6, 10.0

後処理

  1. customis placed in a refrigerator overnight
  2. customthe organic layer is separated
  3. extractionThe aqueous layer is extracted with EtOAc (3×150 mL)
  4. washThe combined organic layers are washed with water (100 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue is purified over silica (EtOAc/Hexane, 1:2)

出典と根拠

ORDレコード
ord-9c4a08dcf33247379ad2c5ac4efe8320
出典データセット
uspto-grants-2006_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07132539B2

反応ノート

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