3-Aminopropionitrile → (2R,4S)-5-biphenyl-4-yl-4-[3-(2-cyano-ethylcarbamoyl)-propionylamino]-2-methyl pentanoic acid ethyl ester

HRID 1469659

反応式

HRID 1469659 の反応式
[CH2:1]([O:3][C:4](=[O:30])[C@H:5]([CH3:29])[CH2:6][C@H:7]([NH:21][C:22](=[O:28])[CH2:23][CH2:24][C:25](O)=[O:26])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH3:2].CCN=C=NCCCN(C)C.Cl.C1C=NC2N(O)N=NC=2C=1.[NH2:53][CH2:54][CH2:55][C:56]#[N:57].C(N(CC)CC)C.NC(C)C#N>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:30])[C@H:5]([CH3:29])[CH2:6][C@H:7]([NH:21][C:22](=[O:28])[CH2:23][CH2:24][C:25](=[O:26])[NH:57][CH2:56][CH2:55][C:54]#[N:53])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH3:2]

参加物

9

反応物 6

HCID 16473-AminopropionitrileHCID 8471Triethylamine2 回HCID 181649HOAt2 回HCID 411840Propanenitrile, 2-amino-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2 回HCID 9811834Sacubitril

生成物 1

HCID 59608195(2R,4S)-5-biphenyl-4-yl-4-[3-(2-cyano-ethylcarbamoyl)-propionylamino]-2-methyl pentanoic acid ethyl ester

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

To a solution of (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester (prepared by using the procedure described in US005217996) (200 mg, 0.486 mmol) in DMF (3 mL) are added EDC-HCl (112 mg, 0.583 mmol) and HOAt (79 mg, 0.583 mmol) at room temperature. After stirring for 10 minutes, 3-aminopropionitrile (41 mg, 0.583 mmol) and triethylamine (0.081 mL, 0.583 mmol) is added and stirred overnight. Additional EDC-HCl (66 mg, 0.292 mmol), HOAt (40 mg, 0.292 mmol), aminopropionitrile (21 mg, 0.292 mmol), and triethylamine (0.081 mL, 0.583 mmol) are added. After stirring for 1 hour, the reaction mixture is heated to 50° C. and stirred for 5 hours. The reaction mixture is diluted with ethyl acetate and washed with H2O and brine. The organic layer is dried over Na2SO4 and concentrated. The residue is purified by silica gel column chromatography to give (2R,4S)-5-biphenyl-4-yl-4-[3-(2-cyano-ethylcarbamoyl)-propionylamino]-2-methyl pentanoic acid ethyl ester. HPLC Retention time 1.37 minutes (condition B); MS 464 (M+1);

後処理

  1. stirringstirred overnight
  2. stirringAfter stirring for 1 hour
  3. stirringstirred for 5 hours
  4. washwashed with H2O and brine
  5. dry with materialThe organic layer is dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-4c8d7bf67a02484696723141223a50da
出典データセット
uspto-grants-2015_04
特許番号
US09006249B2

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