1-Hydroxybenzotriazole → methyl N-{5-[(N-acetyl-4-amino-3-isopropylphenylalanyl)amino]pentanoyl}methioninate

HRID 488653ノート

反応式

HRID 488653 の反応式
[C:1]([NH:4][C@H:5]([C:17]([O:19]C)=O)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[C:9]([CH:14]([CH3:16])[CH3:15])[CH:8]=1)(=[O:3])[CH3:2].[CH3:21][O:22][C:23](=[O:37])[CH:24]([NH:29][C:30](=[O:36])[CH2:31][CH2:32][CH2:33][CH2:34][NH2:35])[CH2:25][CH2:26][S:27][CH3:28].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>[OH-].[Na+].CO.CN(C=O)C.O.C(N(CC)CC)C>[C:1]([NH:4][C@H:5]([C:17]([NH:35][CH2:34][CH2:33][CH2:32][CH2:31][C:30]([NH:29][C@H:24]([C:23]([O:22][CH3:21])=[O:37])[CH2:25][CH2:26][S:27][CH3:28])=[O:36])=[O:19])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[C:9]([CH:14]([CH3:15])[CH3:16])[CH:8]=1)(=[O:3])[CH3:2]

参加物

10

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69803103methyl N-acetyl-4-amino-3-isopropylphenylalaninateHCID 865853262-(5-Amino-pentanoylamino)-4-methylsulfanyl-butyric acid methyl ester

生成物 1

HCID 69799946methyl N-{5-[(N-acetyl-4-amino-3-isopropylphenylalanyl)amino]pentanoyl}methioninate

試薬・触媒・溶媒 5

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒HCID 14798Sodium Hydroxide溶媒

実験手順

A mixture of methyl N-acetyl-4-amino-3-isopropylphenylalaninate in 1N NaOH (4 mL) and methanol (2 mL) was stirred for 5 hours, concentrated under reduced pressure, taken up in a mixture of ethyl acetate and ethanol (3×30 mL, 1:1), dried (Na2SO4), filtered and concentrated under reduced pressure. MS (ESI) m/z=−263 (M−H)−. To a mixture of the residue (239 mg, 0.833 mmole), 2-(5-amino-pentanoylamino)-4-methylsulfanyl-butyric acid methyl ester (298 mg, 1.0 mmole), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (240 mg, 1.25 mmole) and N-hydroxybenzotriazole (169 mg, 1.25 mmole) in DMF (3 mL) was added triethyl amine (116 μL) and the mixture was stirred for 16 hours. The mixture was diluted with water and extracted with ethyl acetate (2×25 mL) then with chloroform (2×25 mL). The combined organics were dried (MgSO4), filtered, concentrated under reduced pressure and purified on silica gel eluting with 30% methanol/ethyl acetate to provide the titled compound (316 mg). MS (ESI) m/z=+509(M+H)+, 531 (M+Na)+.

後処理

  1. concentrationconcentrated under reduced pressure
  2. additiontaken up in a mixture of ethyl acetate and ethanol (3×30 mL, 1:1)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. stirringthe mixture was stirred for 16 hours
  7. extractionextracted with ethyl acetate (2×25 mL)
  8. dry with materialThe combined organics were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. custompurified on silica gel eluting with 30% methanol/ethyl acetate

出典と根拠

ORDレコード
ord-dbb6c06d5f2248ddb9183a5e73c040cd
出典データセット
uspto-grants-2005_12
特許番号
US06972340B2

反応ノート

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