Chlorotrimethylsilane → HCID 66815277, compound

HRID 227158Notes

Reaction equation

HRID 227158 reaction equation
[NH2:1][C@H:2]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33](=[O:41])[N:34]([CH2:38][CH2:39][OH:40])[CH2:35][CH2:36][OH:37])=[CH:27][CH:26]=1)[C:3]([NH:5][C@H:6]([C:15]1[NH:19][C:18]2[CH:20]=[C:21]([I:24])[CH:22]=[CH:23][C:17]=2[N:16]=1)[C@H:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:8])=[O:4].C(N(CC)CC)C.[CH3:49][Si:50](Cl)([CH3:52])[CH3:51].C(OCC)(=O)C>O1CCCC1>[NH2:1][C@H:2]([C:25]1[CH:26]=[CH:27][C:28]([O:31][CH2:32][C:33](=[O:41])[N:34]([CH2:38][CH2:39][O:40][Si:50]([CH3:52])([CH3:51])[CH3:49])[CH2:35][CH2:36][O:37][Si:50]([CH3:52])([CH3:51])[CH3:49])=[CH:29][CH:30]=1)[C:3]([NH:5][C@H:6]([C:15]1[NH:19][C:18]2[CH:20]=[C:21]([I:24])[CH:22]=[CH:23][C:17]=2[N:16]=1)[C@H:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:8])=[O:4]

Participants

6

Reactant 4

HCID 6397Chlorotrimethylsilane2×HCID 8471Triethylamine2×HCID 8857Ethyl AcetateHCID 66815235HCID 66815235, compound

Product 1

HCID 66815277HCID 66815277, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(R)-2-Amino-2-(4-{[bis-(2-hyd roxy-ethyl )-carbamoyl]-methoxy}-phenyl)-N-[(1S,2S)-1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propyl]-acetamide (170 mg, 0.253 mmol) was dissolved in dry tetrahydrofuran (3.4 mL) and cooled in an ice bath. To this solution was added triethylamine (176.3 μL, 1.265 mmol) followed by trimethylsilyl chloride (132 μL, 1.012 mmol). After 0.5 hours another 2.5 equivalents of triethylamine (88 μL, 0.63 mmol) and 2 equivalents of trimethylsilyl chloride (66 μL, 0.506 mmol) were added. The reaction mixture was stirred at 0° C. for an additional 1.5 hours then the reaction mixture was poured into ethyl acetate (40 mL) and washed with brine (3×25 mL). The combine aqueous washes were then extracted with ethyl acetate (2×25 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to give (R)-2-amino-2-(4-{[bis-(2-trimethylsilanyloxy-ethyl)-carbamoyl]-methoxy}-phenyl)-N-[(1S,2S)-1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propyl]-acetamide (190 mg, 92%).

Workup

  1. temperaturecooled in an ice bath
  2. washwashed with brine (3×25 mL)
  3. extractionThe combine aqueous washes were then extracted with ethyl acetate (2×25 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d9dcca437c894110803a713e916009f4
Source dataset
uspto-grants-2009_07
Patent number
US07557221B2

Reaction notes

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