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 931401Notes

Reaction equation

HRID 931401 reaction equation
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

Participants

6

Reactant 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×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×

Product 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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(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.

Workup

  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

Sources & evidence

ORD record
ord-2aa00f794fa64ca7b44f3d1825f9e1bb
Source dataset
uspto-grants-2016_03
Patent number
US09296750B2

Reaction notes

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