Diphenylphosphinic chloride → HCID 131735251, compound

HRID 627022Notes

Reaction equation

HRID 627022 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:24]([CH3:26])[CH3:25])[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].C(N(C(C)C)CC)(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[F:51][C:52]1[CH:58]=[CH:57][CH:56]=[C:55]([F:59])[C:53]=1[NH2:54].OS([O-])(=O)=O.[K+]>C(Cl)Cl>[F:51][C:52]1[CH:58]=[CH:57][CH:56]=[C:55]([F:59])[C:53]=1[NH:54][C:21]([C@H:13]1[N:12]([C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH:24]([CH3:25])[CH3:26])[C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:15]2[CH2:14]1)=[O:22].[F:51][C:52]1[CH:58]=[CH:57][CH:56]=[C:55]([F:59])[C:53]=1[NH:54][C:21]([C@H:13]1[N:12]([C:10](=[O:11])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH:24]([CH3:25])[CH3:26])[C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:15]2[CH2:14]1)=[O:22]

Participants

8

Reactant 5

HCID 73910Diphenylphosphinic chlorideHCID 796472,6-DifluoroanilineHCID 81531DiisopropylethylamineHCID 516920Potassium bisulfateHCID 118354538HCID 118354538, compound

Product 2

HCID 131735251HCID 131735251, compoundHCID 131735252HCID 131735252, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (260 mg, 715 μmol, Eq: 1.00) and diisopropylethylamine (375 μL, 2.15 mmol, Eq: 3) in DCM (7.8 mL) was added diphenylphosphinic chloride (372 mg, 300 μL, 1.57 mmol, Eq: 2.2). After stirring for 5 min, 2,6-difluoroaniline (109 μL, 1.07 mmol, Eq: 1.5) was added and the resulting solution was stirred at rt overnight. The reaction mixture was poured into 0.1 M aqueous KHSO4 (20 mL) and the resulting mixture was extracted with EtOAc. The organic layers were concentrated in vacuo and the crude material was purified by flash chromatography (silica gel, 40 g, 0% to 30% EtOAc in hexanes) to give tert-butyl (S)-1-((S)-2-(2,6-difluorophenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (100 mg) and tert-butyl (R)-1-((S)-2-(2,6-difluorophenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate white solid (80 mg), m/z=497 (M+Na).

Workup

  1. stirringthe resulting solution was stirred at rt overnight
  2. extractionthe resulting mixture was extracted with EtOAc
  3. concentrationThe organic layers were concentrated in vacuo
  4. customthe crude material was purified by flash chromatography (silica gel, 40 g, 0% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2ae6209821fb45d3b0d1455d45740cfd
Source dataset
uspto-grants-2016_04
Patent number
US09309248B2

Reaction notes

Loading…