Trimethyl orthoformate → 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-tetrazol-1-yl-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester

HRID 2362210ノート

反応式

HRID 2362210 の反応式
[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][C:7]1[N:8]([C:19]2[CH:24]=[CH:23][C:22]([C:25](=[O:27])[NH2:26])=[CH:21][C:20]=2[CH3:28])[C:9]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)=[CH:10][CH:11]=1)[CH3:2].[CH3:30]OC(OC)OC.[N-:37]=[N+:38]=[N-:39].[Na+]>C(O)(=O)C.O>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][C:7]1[N:8]([C:19]2[CH:24]=[CH:23][C:22]([C:25](=[O:27])[NH2:26])=[CH:21][C:20]=2[CH3:28])[C:9]([C:12]2[CH:13]=[CH:14][C:15]([N:18]3[CH:30]=[N:39][N:38]=[N:37]3)=[CH:16][CH:17]=2)=[CH:10][CH:11]=1)[CH3:2]

参加物

6

反応物 3

HCID 9005Trimethyl orthoformateHCID 33557Sodium AzideHCID 583056233-[5-(4-aminophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl]propanoic acid ethyl ester

生成物 1

HCID 583056923-[1-(4-carbamoyl-2-methylphenyl)-5-(4-tetrazol-1-yl-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester収率 60%

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 962Water溶媒

実験手順

Under a nitrogen atmosphere, 3-[5-(4-aminophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester (11A, synthesis described in Scheme 4 where R1=4-carbamoyl-2-methylphenyl) (102 mg, 0.26 mmol) was dissolved in 2 mL glacial acetic acid. Trimethylorthoformate (0.1 mL, 0.78 mmol) was added. The mixture was stirred for 20 min. at room temperature. Sodium azide (25 mg, 0.39 mmol) was added and the reaction was heated to 80° C. for 2 hrs. After cooling, the reaction was diluted with water (3 mL) and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by preparative TLC plate (1500 microns, 10% IPA/CH2Cl2). The desired band (rf=0.5) was isolated and dried under high vacuum to yield 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-tetrazol-1-yl-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester (12B) (71 mg, 60%, light orange powder).

後処理

  1. temperaturethe reaction was heated to 80° C. for 2 hrs
  2. temperatureAfter cooling
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by preparative TLC plate (1500 microns, 10% IPA/CH2Cl2)
  9. customThe desired band (rf=0.5) was isolated
  10. customdried under high vacuum

出典と根拠

ORDレコード
ord-899578f1e1374a8bb0ecf9903d1f063b
出典データセット
uspto-grants-2014_04
特許番号
US08691816B2

反応ノート

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