Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → methyl[(2S)-1-({2-[(3S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(diphenyl)silyl]oxy}butyl]phenyl}amino)-1-oxo-3,3-diphenylpropan-2-yl]carbamate

HRID 714128Notes

Reaction equation

HRID 714128 reaction equation
[C:1]([O:5][C:6](=[O:37])[NH:7][C@@H:8]([CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[NH2:36])[CH2:9][O:10][Si:11]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:38][O:39][C:40]([NH:42][C@H:43]([C:57](O)=[O:58])[CH:44]([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:41].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C1C=CN=CC=1)C>[CH3:38][O:39][C:40](=[O:41])[NH:42][C@@H:43]([CH:44]([C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)[C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)[C:57]([NH:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[CH2:29][CH2:28][C@H:8]([NH:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:37])[CH2:9][O:10][Si:11]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:58]

Participants

5

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10017620(S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acidHCID 68029214tert-butyl[(2S)-4-(2-aminophenyl)-1-{[tert-butyl(diphenyl)silyl]oxy}butan-2-yl]carbamate

Product 1

HCID 68029329methyl[(2S)-1-({2-[(3S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(diphenyl)silyl]oxy}butyl]phenyl}amino)-1-oxo-3,3-diphenylpropan-2-yl]carbamateYield 82%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

A mixture of tert-butyl[(2S)-4-(2-aminophenyl)-1-{[tert-butyl(diphenyl)silyl]oxy}butan-2-yl]carbamate (5, 242 mg, 0.466 mmol), N-(methoxycarbonyl)-β-phenyl-L-phenylalanine (6, 225 mg, 0.752 mmol) (or any other suitable carboxylic acid), HATU (318 mg, 0.836 mmol) and DMAP (50 mg, 0.409 mmol) was dissolved in dry Py (2 ml) and the mixture was stirred at room temperature under N2 for 13 h. Quenched with water (0.5 mL), then diluted (DCM), washed with 5% KHSO4 in water, then saturated NaHCO3, dried over MgSO4, filtered and concentrated. Purified through a chromatographic cartridge of silicagel (12 g) eluted with 10% to 30% EtOAc in hexane to give 305 mg (82% yield) of title compound as white foam, MS: m/z=822.2 (MNa+).

Workup

  1. dissolutionwas dissolved in dry Py (2 ml)
  2. customQuenched with water (0.5 mL)
  3. additiondiluted (DCM)
  4. washwashed with 5% KHSO4 in water
  5. dry with materialsaturated NaHCO3, dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurified through a chromatographic cartridge of silicagel (12 g)
  9. washeluted with 10% to 30% EtOAc in hexane

Sources & evidence

ORD record
ord-cf44c8abc1154c6185995274722527f3
Source dataset
uspto-grants-2015_11
Patent number
US09187415B2

Reaction notes

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