Diisopropylethylamine → HCID 131735270, compound

HRID 627053Notes

Reaction equation

HRID 627053 reaction equation
[NH2:1][C@@H:2]([CH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)[C:3]([N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[CH2:7][CH:6]1[C:14]([NH:16][C:17]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=1[F:24])=[O:15])=[O:4].[C:31]([O:35][C:36]([N:38]([CH3:44])[C@@H:39]([CH3:43])[C:40](O)=[O:41])=[O:37])([CH3:34])([CH3:33])[CH3:32].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[F:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:17]=1[NH:16][C:14]([CH:6]1[N:5]([C:3](=[O:4])[C@@H:2]([NH:1][C:40](=[O:41])[C@@H:39]([N:38]([CH3:44])[C:36](=[O:37])[O:35][C:31]([CH3:32])([CH3:34])[CH3:33])[CH3:43])[CH:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[CH2:7]1)=[O:15]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118380536HCID 118380536, compound

Product 1

HCID 131735270HCID 131735270, compoundYield 101%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-((S)-2-amino-2-(tetrahydropyran-4-yl)acetyl)-N-(2,6-difluorophenyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxamide (37 mg, 88.9 μmol, Eq: 1.00), (S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid (27.1 mg, 133 μmol, Eq: 1.5) and diisopropyl-ethylamine (62 μL, 355 μmol, Eq: 4) in DMF was added HATU (60.8 mg, 160 μmol, Eq: 1.8) and the resulting solution was stirred at rt. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL). The organic layer was then washed with 0.1 M aqueous NaOH and brine and then concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 100% EtOAc in hexanes) to give tert-butyl (2S)-1-((1S)-2-(2-(2,6-difluorophenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-2-oxo-1-(tetrahydro-2 h-pyran-4-yl)ethylamino)-1-oxopropan-2-yl(methyl)carbamate (54 mg), m/z=602 (M+H).

Workup

  1. extractionextracted with EtOAc (10 mL)
  2. washThe organic layer was then washed with 0.1 M aqueous NaOH and brine
  3. concentrationconcentrated in vacuo
  4. customThe crude material was purified by flash chromatography (silica gel, 12 g, 0% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-58ee31b4190543fd9dbfcf42d4e72db4
Source dataset
uspto-grants-2016_04
Patent number
US09309248B2

Reaction notes

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