Diisopropylethylamine → N-[(3S,5S,6R)-6-Methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl]-2'-oxo-1',2'-dihydro-3H-spiro[1-benzofuran-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

HRID 931401ノート

反応式

HRID 931401 の反応式
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)[C:12]2C=CC=C[C:11]=2N=N1.[O:28]=[C:29]1[N:37](COCC[Si](C)(C)C)[C:32]2=[N:33][CH:34]=[CH:35][CH:36]=[C:31]2[C:30]21[O:56][C:48]1=NC=[C:51]([C:53]([OH:55])=O)[CH:52]=[C:47]1[CH2:46]2.Cl.[NH2:58][C@H:59]1[CH2:64][C@@H:63]([C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[C@@H:62]([CH3:71])[N:61]([CH2:72][C:73]([F:76])([F:75])[F:74])[C:60]1=[O:77].C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH3:71][C@H:62]1[N:61]([CH2:72][C:73]([F:74])([F:75])[F:76])[C:60](=[O:77])[C@@H:59]([NH:58][C:53]([C:51]2[CH:11]=[CH:12][C:48]3[O:56][C:30]4([C:31]5[C:32](=[N:33][CH:34]=[CH:35][CH:36]=5)[NH:37][C:29]4=[O:28])[CH2:46][C:47]=3[CH:52]=2)=[O:55])[CH2:64][C@H:63]1[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68749751(3S,5S,6R)-3-amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-one hydrochloride2 回HCID 900505402'-Oxo-1'-((2-(trimethylsilyl)ethoxy)methyl)-1',2'-dihydro-3H-spiro[furo[2,3-b]pyridine-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxylic acid2 回

生成物 1

HCID 90050663N-[(3S,5S,6R)-6-Methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl]-2'-oxo-1',2'-dihydro-3H-spiro[1-benzofuran-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

(Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (90 mg, 0.20 mmol) is added to a solution of 2′-oxo-1′,2′-dihydro-3H-spiro[benzofuran-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid (described in Intermediate 2) (48 mg, 0.17 mmol), (3S,5S,6R)-3-amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-one hydrochloride (described in Intermediate 1, 54 mg, 0.17 mmol), and N,N-diisopropylethylamine (0.15 mL, 0.84 mmol) in DMF (3 mL), and the resulting mixture is stirred at ambient temperature for 3 h. The reaction mixture is then partitioned between saturated aqueous sodium bicarbonate solution (20 mL) and ethyl actetate (3×20 mL). The combined organic layers are washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue is purified by flash column chromatography on silica gel, eluting with a gradient of CH2Cl2:MeOH—100:0 to 90:10, to afford the title compound as a mixture of diastereomers.

後処理

  1. customThe reaction mixture is then partitioned between saturated aqueous sodium bicarbonate solution (20 mL) and ethyl actetate (3×20 mL)
  2. washThe combined organic layers are washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by flash column chromatography on silica gel
  6. washeluting with a gradient of CH2Cl2

出典と根拠

ORDレコード
ord-2aa00f794fa64ca7b44f3d1825f9e1bb
出典データセット
uspto-grants-2016_03
特許番号
US09296750B2

反応ノート

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