Dimethylamine → 2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-N,N-dimethyl-2-oxoacetamide

HRID 577872Notes

Reaction equation

HRID 577872 reaction equation
[Si:1]([O:18][CH2:19][C:20]1[C:21]([N:33]2[CH2:38][C@H:37]([CH3:39])[O:36][C@H:35]([CH3:40])[CH2:34]2)=[C:22]([F:32])[C:23]([F:31])=[C:24]([C:26](=[O:30])[C:27]([OH:29])=O)[CH:25]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:41][N:42](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:43].F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.CNC>C1COCC1.CN(C=O)C.O>[Si:1]([O:18][CH2:19][C:20]1[C:21]([N:33]2[CH2:38][C@H:37]([CH3:39])[O:36][C@H:35]([CH3:40])[CH2:34]2)=[C:22]([F:32])[C:23]([F:31])=[C:24]([C:26](=[O:30])[C:27]([N:42]([CH3:43])[CH3:41])=[O:29])[CH:25]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866580682-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetic acid2×

Product 1

HCID 866580702-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-N,N-dimethyl-2-oxoacetamideYield 74.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetic acid (Intermediate 118, 250 mg, 0.44 mmol), HATU (335 mg, 0.88 mmol), triethylamine (0.184 ml, 1.32 mmol) and 2.0M dimethylamine (0.440 ml, 0.88 mmol) in THF were stirred in DMF (5 ml) in a closed vial for 16 hours. The reaction was diluted with water and extracted 3× with ethyl acetate. The organic layers were washed 3× with brine, dried over MgSO4 and concentrated to give an oil. The oil was purified by silica gel column chromatography using a gradient of hexanes to ethyl acetate. Fractions were combined and concentrated to give the title compound (195 mg, 0.328 mmol, 74.5%)

Workup

  1. extractionextracted 3× with ethyl acetate
  2. washThe organic layers were washed 3× with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customto give an oil
  6. customThe oil was purified by silica gel column chromatography
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-7145708601f04c9fabaf7c6d78756345
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

Loading…