3-Aminopropionitrile → (R)-4-biphenyl-4-yl-3-[3-(2-cyano-ethylcarbamoyl)-propionylamino]-butyric acid ethyl ester

HRID 70866

反応式

HRID 70866 の反応式
[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C@H:6]([NH:20][C:21](=[O:27])[CH2:22][CH2:23][C:24](O)=[O:25])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)[CH3:2].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[NH2:51][CH2:52][CH2:53][C:54]#[N:55]>C1COCC1>[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C@H:6]([NH:20][C:21](=[O:27])[CH2:22][CH2:23][C:24](=[O:25])[NH:55][CH2:54][CH2:53][C:52]#[N:51])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)[CH3:2]

参加物

6

反応物 4

HCID 16473-Aminopropionitrile2 回HCID 757711-Hydroxybenzotriazole2 回HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2 回HCID 49822223(R)-4-biphenyl-4-yl-3-(3-carboxy-propionylamino)-butyric acid ethyl ester

生成物 1

HCID 67208765(R)-4-biphenyl-4-yl-3-[3-(2-cyano-ethylcarbamoyl)-propionylamino]-butyric acid ethyl ester収率 96%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Next, to a solution of (R)-4-biphenyl-4-yl-3-(3-carboxy-propionylamino)-butyric acid ethyl ester (200 mg, 0.522 mmol) in THF (10 mL) at room temperature is added EDC HCl (120 mg, 0.626 mmol) and HOBT (96 mg, 0.626 mmol). The reaction is stirred at room temperature for 10 minutes then added 3-aminopropionitrile (0.046 ml, 0.626 mmol) and TEA (0.087 ml, 0.626 mmol). After 1 hour, 0.5 equivalent of EDC HCl, HOBT, and 3-aminopropionitrile are added and stirred for 16 hours. The reaction mixture is quenched by brine and is extracted with ethylacetate. The combined organic layer is washed with brine and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The obtained residue is purified by flash chromatography (silica gel, 2% to 5% EtOH/DCM) to give (R)-4-biphenyl-4-yl-3-[3-(2-cyano-ethylcarbamoyl)-propionylamino]-butyric acid ethyl ester (218 mg, 96% yield). HPLC retention time=0.77 minutes (condition E); MS=436 (m+1).

後処理

  1. waitAfter 1 hour
  2. stirringstirred for 16 hours
  3. customThe reaction mixture is quenched by brine
  4. extractionis extracted with ethylacetate
  5. washThe combined organic layer is washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe obtained residue is purified by flash chromatography (silica gel, 2% to 5% EtOH/DCM)

出典と根拠

ORDレコード
ord-2d4d108ae8a44645926ed110e1bb7ffd
出典データセット
uspto-grants-2014_09
特許番号
US08822534B2

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