Formaldehyde → [(S)-7-Cyano-4-((2R,3R)-3-hydroxy-1-methyl-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester

HRID 449843ノート

反応式

HRID 449843 の反応式
Cl.[CH:2]([O:5][C:6](=[O:29])[NH:7][C@@H:8]1[CH2:28][C:11]2[N:12]([CH2:21][C@@H:22]3[C@H:26]([OH:27])[CH2:25][CH2:24][NH:23]3)[C:13]3[CH:14]=[CH:15][C:16]([C:19]#[N:20])=[CH:17][C:18]=3[C:10]=2[CH2:9]1)([CH3:4])[CH3:3].C=O.[C:32](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(#N)C.C(OCC)(=O)C.CO>[CH:2]([O:5][C:6](=[O:29])[NH:7][C@@H:8]1[CH2:28][C:11]2[N:12]([CH2:21][C@@H:22]3[C@H:26]([OH:27])[CH2:25][CH2:24][N:23]3[CH3:32])[C:13]3[CH:14]=[CH:15][C:16]([C:19]#[N:20])=[CH:17][C:18]=3[C:10]=2[CH2:9]1)([CH3:4])[CH3:3]

参加物

8

反応物 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 66933117[(S)-7-Cyano-4-((2R,3R)-3-hydroxy-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester hydrochloride

生成物 1

HCID 66933305[(S)-7-Cyano-4-((2R,3R)-3-hydroxy-1-methyl-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester収率 61%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of [(S)-7-cyano-4-((2R,3R)-3-hydroxy-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester hydrochloride salt (380 mg, 907.1 μmol) in acetonitrile (50 mL) is treated with methanol (5 mL) until most of the solid is dissolved and then treated with formaldehyde (136.3 μL, 1.81 mmol) and sodium triacetoxyborohydride (400.5 mg, 1.81 mmol). The reaction is stirred at room temperature overnight. Saturated aqueous sodium bicarbonate solution (50 mL) is added and stirred for 30 min. The mixture is diluted with ethyl acetate (120 mL) and the resulting suspension is washed with water (3×100 mL) and brine. The organic portion is dried over sodium sulfate, filtered, and concentrated to dryness. The residue is purified by medium pressure liquid chromatography, eluting with methanol:chloroform (5:95). Fractions containing pure product are combined and concentrated to afford 0.2 g (61%) of the title compound. LC-ES/MS m/z 397.2 [M+H]+, TR=1.87 min.

後処理

  1. dissolutionis dissolved
  2. stirringstirred for 30 min
  3. washthe resulting suspension is washed with water (3×100 mL) and brine
  4. dry with materialThe organic portion is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue is purified by medium pressure liquid chromatography
  8. washeluting with methanol:chloroform (5:95)
  9. additionFractions containing pure product
  10. concentrationconcentrated

出典と根拠

ORDレコード
ord-522ee113492d4d8597265a4f04041d8d
出典データセット
uspto-grants-2013_07
特許番号
US08486943B2

反応ノート

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