Isobutyl chloroformate → {[6,7-Dimethoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carbonyl]-amino}-acetic acid ethyl ester

HRID 1833272ノート

反応式

HRID 1833272 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([C:15](=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=1)=[N:8][CH:7]=[C:6]2[C:25]([OH:27])=O.C(OC(Cl)=O)C(C)C.Cl.[CH2:37]([O:39][C:40](=[O:43])[CH2:41][NH2:42])[CH3:38]>CN(C)C=O.C(N(CC)CC)C.C(OCC)(=O)C>[CH2:37]([O:39][C:40](=[O:43])[CH2:41][NH:42][C:25]([C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]([C:15](=[O:24])[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=2)=[N:8][CH:7]=1)=[O:27])[CH3:38]

参加物

7

反応物 3

HCID 62365Isobutyl chloroformateHCID 2723640Glycine ethyl ester, hydrochlorideHCID 11394498HCID 11394498、化合物

生成物 1

HCID 11155195{[6,7-Dimethoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carbonyl]-amino}-acetic acid ethyl ester収率 6.3%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒2 回HCID 8471Triethylamine溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

A solution of 6,7-dimethoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carboxylic acid (30.0 mg, 81.65 mmol) in dry, N,N-dimethylformamide (2 mL) chilled in an ice-bath under argon. With stirring, triethylamine (14.4 uL, 102 mmol) and isobutylchloroformate (13.4 uL, 102 mmol) were added. The solution was stirred for 30 min and then solution of glycine ethyl ester hydrochloride (227 mg, 1,633 mM) in 4 mL of dimethylformamide and triethylamine (0.229 mL, 1.633 mM) were added and the reaction was allowed to warm to room temperature with stirring for 1 hr. and then diluted with ethyl acetate (30 mL), The ethyl acetate solution was washed sequentially with saturated sodium bicarbonate solution (2×5 mL), water (5 mL), and saturated sodium chloride solution (5 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to afford 46 mg solid. This crude material was purified by flash chromatography, eluting with 50% ethyl acetate in hexanes (containing 1% acetic acid) and then increasing gradually to 80% ethyl acetate in hexanes After tlc analysis, fractions were pooled and evaporated to yield 36 mg (79.4%) of white, powder as an acetate salt: APCI-MS m/e calcd for C24H24N2O7 (M+H) 453.5, found 453; H NMR (300 MHz) compatible

後処理

  1. stirringThe solution was stirred for 30 min
  2. stirringwith stirring for 1 hr
  3. washThe ethyl acetate solution was washed sequentially with saturated sodium bicarbonate solution (2×5 mL), water (5 mL), and saturated sodium chloride solution (5 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-d0028e7035f94d3b8c70da64ed61ddc0
出典データセット
uspto-grants-2006_06
特許番号
US07067529B2

反応ノート

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