Dimethylformamide → {1-[2-[2-Ethyl-4-(1-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-1-(4-fluorobenzyl)-2-oxo-ethyl carbamoyl]-1-methyl-ethyl}-carbamic acid tert-butyl ester

HRID 720187노트

반응식

HRID 720187 반응식
Cl.[NH2:2][CH:3]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1)[C:4]([N:6]1[CH2:11][CH2:10][N:9]([CH:12]([CH2:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)[C:13]([NH:15][CH3:16])=[O:14])[CH2:8][CH:7]1[CH2:28][CH3:29])=[O:5].[C:38]([O:42][C:43](CC(N)(C)C(O)=O)=[O:44])([CH3:41])([CH3:40])[CH3:39].O[N:53]1[C:57]2[CH:58]=CC=C[C:56]=2N=N1.CN1CCOCC1.CN([CH:72]=[O:73])C>O.CCOC(C)=O>[C:38]([O:42][C:43](=[O:44])[NH:53][C:57]([C:72](=[O:73])[NH:2][CH:3]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1)[C:4]([N:6]1[CH2:11][CH2:10][N:9]([CH:12]([C:13](=[O:14])[NH:15][CH3:16])[CH2:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)[CH2:8][CH:7]1[CH2:28][CH3:29])=[O:5])([CH3:58])[CH3:56])([CH3:39])([CH3:40])[CH3:41]

참가 물질

8

반응물 5

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 19692748Boc-aminoisobutyric acidHCID 219015482-{4-[2-amino-3-(4-fluorophenyl)-propionyl]-3-ethyl-piperazin-1-yl}-N-methyl-3-naphthalen-2-yl-propioamide Hydrochloride

생성물 1

HCID 69587967{1-[2-[2-Ethyl-4-(1-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-1-(4-fluorobenzyl)-2-oxo-ethyl carbamoyl]-1-methyl-ethyl}-carbamic acid tert-butyl ester

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

2-{4-[2-Amino-3-(4-fluorophenyl)-propionyl]-3-ethyl-piperazin-1-yl}-N-methyl-3-naphthalen-2-yl-propioamide hydrochloride, 41, (0.3 g, 0.6 mmol) and tert-butyloxycarbonyl-α-aminoisobutyric acid (AIB) (0.12 g, 0.6 mmol) 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide (0.22 g, 1.1 mmol) and 1-hydroxybenzotriazole (0.1 g, 0.7 mmol) are dissolved in anhydrous DMF (2.5 mL). The reaction mixture is cooled to 0° C., then N-methylmorpholine (0.2 mL, 1.7 mmol) is added. The reaction mixture is placed in refrigerator overnight. EtOAc (25 mL) and water (75 mL) are added, and the organic layer is separated. The aqueous layer is extracted with EtOAc (3×30 mL). All organic layers are combined and washed with water (2×50 mL), and dried over Na2SO4. Solvent is removed in vacuo and the product is purified over silica (EtOAc/Hexane, 2/1) to afford 0.7 g of the desired compound. 1H NMR (CDCl3, δ): 7.80–7.58 (m, 4H), 7.42–7.22 (m, 3H), 7.20–7.00 (m, 2H), 6.98–6.50 (m, 2H), 5.40–4.98 (m, 1.5H), 4.70–3.90 (m, 1H), 3.75–3.02 (m, 3.5H), 3.00–2.56 (m, 7H), 2.42–2.35 (m, 1H), 2.18–1.95 (m, 2.5H), 1.50–1.12 (m, 18H), 0.095–0.75 (m, 3H); 13C NMR, δ 174.4, 172.1, 171.9, 170.3, 169.6, 163.7, 162.0, 154.6, 137.3, 133.7, 132.3, 131.4, 130.8, 128.1, 127.8, 127.6, 126.2, 125.6, 115.7, 115.4, 115.2, 80.0, 70.2, 56.7, 55.3, 50.9, 50.0, 49.9, 41.8, 39.5, 38.5, 37.9, 32.7, 32.4, 28.5, 28.3, 26.1, 25.5, 25.3, 23.1, 22.1, 10.6, 10.1.

후처리

  1. customis placed in refrigerator overnight
  2. customthe organic layer is separated
  3. extractionThe aqueous layer is extracted with EtOAc (3×30 mL)
  4. washwashed with water (2×50 mL)
  5. dry with materialdried over Na2SO4
  6. customSolvent is removed in vacuo
  7. customthe product is purified over silica (EtOAc/Hexane, 2/1)

출처 및 근거

ORD 기록
ord-2e2e6a967bba42189526f6b6596aa56e
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07132539B2

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