Diisopropylethylamine → N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-methyl-5-phenyl-1H-pyrrole-2-carboxamide

HRID 1359659ノート

反応式

HRID 1359659 の反応式
Cl.Cl.[NH2:3][C@@H:4]1[CH:9]2[CH2:10][CH2:11][N:6]([CH2:7][CH2:8]2)[CH2:5]1.CCN(C(C)C)C(C)C.[CH3:21][N:22]1[C:26]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:25][CH:24]=[C:23]1[C:33](O)=[O:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1.C(Cl)Cl>[N:6]12[CH2:11][CH2:10][CH:9]([CH2:8][CH2:7]1)[C@@H:4]([NH:3][C:33]([C:23]1[N:22]([CH3:21])[C:26]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:25][CH:24]=1)=[O:34])[CH2:5]2

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12494972(R)-(+)-3-Aminoquinuclidine DihydrochlorideHCID 223507001-methyl-5-phenyl-1H-pyrrole-2-carboxylic acid

生成物 1

HCID 9815147N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-methyl-5-phenyl-1H-pyrrole-2-carboxamide収率 31.1%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of (R)-(+)-3-aminoquinuclidine dihydrochloride (0.831 g, 4.17 mmol) in 55 mL of dry THF is added DIEA (2.08 mL, 11.9 mmol). After allowing the mixture to stir under nitrogen for 15 min, the product from Step 152c (0.800 g, X 3.98 mmol) is added. The mixture is allowed to stir for another 15 min, cooled in an A ice bath, and HATU (1.59 g, 4.17 mmol) is added. The reaction mixture is stirred on >an ice bath for 0.5 h, then at rt for an additional 2 h. The mixture is diluted with 60 mL CH2Cl2, washed with 50 mL of 1N NaOH and 50 mL of satd NaHCO3 solution, dried over MgSO4, filtered, and concentrated in vacuo. The crude product is purified by flash column chromatography (10% EtOAc, 1% NH4OH in CH2Cl2) to give 0.383 grams of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-methyl-5-phenyl-1H-pyrrole-2-carboxamide (31%) as a white solid. MS for C19H23N3O (ESI) (M+H)+ m/z 310.3.

後処理

  1. stirringto stir for another 15 min
  2. additionis added
  3. stirringThe reaction mixture is stirred on >an ice bath for 0.5 h
  4. waitat rt for an additional 2 h
  5. washwashed with 50 mL of 1N NaOH and 50 mL of satd NaHCO3 solution
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product is purified by flash column chromatography (10% EtOAc, 1% NH4OH in CH2Cl2)

出典と根拠

ORDレコード
ord-ff51a74cfd0340758f32cc40527a5b84
出典データセット
uspto-grants-2003_07
特許番号
US06599916B2

反応ノート

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