tert-Butyldimethylsilane → HCID 58997413, compound

HRID 1592061Notes

Reaction equation

HRID 1592061 reaction equation
[C:1]([NH:4][C@@H:5]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:6]([NH:8][C@H:9]([C:34](=[O:41])[NH:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N:17]2[CH2:21][C:20](=[O:22])[N:19](CC3C=CC(OC)=CC=3)[S:18]2(=[O:33])=[O:32])[CH:12]=1)=[O:7])(=[O:3])[CH3:2].C([SiH](C)C)(C)(C)C>C(O)(C(F)(F)F)=O.CC#N.O>[C:1]([NH:4][C@@H:5]([CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[C:6]([NH:8][C@H:9]([C:34](=[O:41])[NH:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N:17]2[CH2:21][C:20](=[O:22])[NH:19][S:18]2(=[O:33])=[O:32])[CH:12]=1)=[O:7])(=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 5072427tert-ButyldimethylsilaneHCID 67139666HCID 67139666, compound

Product 1

HCID 58997413HCID 58997413, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of the title H compound, (S)-2-acetylamino-N-((S)-2-{3-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-1-pentylcarbamoyl-ethyl)-3-phenyl-propionamide (124 mg, 0.183 mmol) in TFA (3 mL) containing t-butyidimethylsilane (0.091 mL, 0.548 mmol) is heated at 80° C. for 30 min, then concentrated under nitrogen stream to give an oil containing a fine dark suspension. The product is taken up in 60% MeCN in water and water (1 mL) is added. The mixture filtered through a 0.1 micron Acrodisc filter and the filtrate is loaded onto a preparative reverse phase HPLC column (YMC CombiPrep Pro C18, 50×20 mm I.D., particle size S-5 micron, 12 nM) in five aliquots and eluted at 30 mL/min with a gradient of 90:10 (0.1% TFA in water:MeCN) to 10:90 over 5 min. Then held at 10:90 until 7 min. Fractions containing product are combined and concentrated on a Savant Speedvac to yield (S)-2-acetylamino-N-{(S)-1-pentylcarbamoyl-2-[3-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-phenyl]-ethyl}-3-phenyl-propionamide as a white foam: [M+1]+=558.

Workup

  1. concentrationconcentrated under nitrogen stream
  2. customto give an oil
  3. additioncontaining a fine dark suspension
  4. filtrationThe mixture filtered through a 0.1 micron Acrodisc
  5. filtrationfilter
  6. washeluted at 30 mL/min with a gradient of 90:10 (0.1% TFA in water:MeCN) to 10:90 over 5 min
  7. additionFractions containing product
  8. concentrationconcentrated on a Savant Speedvac

Sources & evidence

ORD record
ord-a52d249ffca44a5db1ced1248c76769d
Source dataset
uspto-grants-2007_11
Patent number
US07291635B2

Reaction notes

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