Aniline → HCID 131735249, compound

HRID 627019Notes

Reaction equation

HRID 627019 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)[C:10]([N:12]1[C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:15]2[CH2:14][CH:13]1[C:21](O)=[O:22])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[NH2:61][C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>O.CN(C=O)C>[CH:24]1([C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:10](=[O:11])[N:12]2[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[CH2:14][C@@H:13]2[C:21](=[O:22])[NH:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 6115AnilineHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118380531HCID 118380531, compound

Product 1

HCID 131735249HCID 131735249, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In a 50 mL round-bottomed flask, 1-((S)-2-(tert-butoxycarbonylamino)-2-cyclohexylacetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (300 mg, 744 μmol, Eq: 1.00) and HATU (339 mg, 892 μmol, Eq: 1.2) were combined with DMF (7 mL) to give a colorless solution. Triethylamine (124 μL, 892 μmol, Eq: 1.2) and aniline (83 mg, 892 μmol, Eq: 1.2) were added and the reaction was stirred at rt overnight. The reaction mixture was poured into water (10 mL) and extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 5% to 25% EtOAc in hexanes) to give tert-butyl (R)-(1S)-1-cyclohexyl-2-oxo-2-(2-(phenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)ethylcarbamate (eluted first, 160 mg) and tert-butyl (S)-(1S)-1-cyclohexyl-2-oxo-2-(2-(phenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)ethylcarbamate (eluted second, 130 mg), m/z=479 (M+H).

Workup

  1. customto give a colorless solution
  2. extractionextracted with EtOAc (2×25 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 24 g, 5% to 25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2fd7e1ab1d9a4b70b50b031ee5bf3771
Source dataset
uspto-grants-2016_04
Patent number
US09309248B2

Reaction notes

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