Water → HCID 54588114, compound

HRID 403454Notes

Reaction equation

HRID 403454 reaction equation
[Si]([O:8][C@H:9]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C@H:10]1[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]3[N:23]=[C:22]([C@@H:24]([N:26]4[CH:31]=[CH:30][CH:29]=[N:28][C:27]4=[O:32])[CH3:25])[NH:21][C:20]=3[CH:33]=2)[N:11]1C(OC(C)(C)C)=O)(C(C)(C)C)(C)C.C(#N)C.O>FC(F)(F)C(O)=O>[OH:8][C@H:9]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C@@H:10]1[NH:11][C@H:12]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]3[N:23]=[C:22]([C@@H:24]([N:26]4[CH:31]=[CH:30][CH:29]=[N:28][C:27]4=[O:32])[CH3:25])[NH:21][C:20]=3[CH:33]=2)[CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 962WaterHCID 6342AcetonitrileHCID 86677204HCID 86677204, compound

Product 1

HCID 54588114HCID 54588114, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 0.017 g (0.026 mmol) of tert-butyl(2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-({2-[(1S)-1-(2-oxopyrimidin-1(2H)-yl)ethyl]-1H-benzimidazo-6-yl}methyl)pyrrolidine-1-carboxylate from Step B above in 2 mL of a 3:3:1 trifluoroacetic acid:acetonitrile:water mixture was stirred at 70° C. for 3 h. All volatiles were removed in vacuo and the crude light brown residue was purified by reverse-phase HPLC (TMC Pro-Pac C18; 10-100% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient) to afford the title compound as a white solid. 1H-NMR (500 MHz, CD3OD) δ 8.85-8.62 (m, 1H), 8.57-8.31 (m, 1H), 7.91-7.65 (m, 2H), 7.64-7.24 (m, 9H), 6.86-6.59 (m, 1H), 6.19-5.87 (m, 1H), 4.85-4.67 (m, 2H), 4.04-3.68 (m, 4H), 3.28-3.10 (m, 2H), 2.30-1.62 (m, 4H). LC/MS: m/z (ES) 430.2 (MH)+.

Workup

  1. customAll volatiles were removed in vacuo
  2. customthe crude light brown residue was purified by reverse-phase HPLC (TMC Pro-Pac C18; 10-100% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient)

Sources & evidence

ORD record
ord-44b233b5423744e085051d1b639c16a8
Source dataset
uspto-grants-2014_06
Patent number
US08748433B2

Reaction notes

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