tert-Butyldimethylsilane → HCID 58997398, compound

HRID 1592050Notes

Reaction equation

HRID 1592050 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][C:14]([N:17]2[CH2:21][C:20](=[O:22])[N:19](CC3C=CC(OC)=CC=3)[S:18]2(=[O:33])=[O:32])=[CH:13][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: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:12]=[CH:13][C:14]([N:17]2[CH2:21][C:20](=[O:22])[NH:19][S:18]2(=[O:33])=[O:32])=[CH:15][CH:16]=1)=[O:7])(=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 5072427tert-ButyldimethylsilaneHCID 67139939HCID 67139939, compound

Product 1

HCID 58997398HCID 58997398, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of the title C compound, (S)-2-acetylamino-N-((S)-2-{4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-1-pentylcarbamoyl-ethyl)-3-phenyl-propionamide (49 mg, 0.07 mmol) in TFA (1.4 mL) containing t-butyldimethylsilane (0.035 mL, 0.21 mmol) is heated at 80° C. for 1 h. The reaction is concentrated under nitrogen stream to give an oil which is taken up in 60% MeCN in water. Water (1 mL) is added, and the mixture filtered through a 0.1 micron Acrodisc filter. The resulting mixture 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 three 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-[4-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-phenyl]-ethyl)-3-phenyl-propionamide as a white solid: [M−1]−=556.

Workup

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

Sources & evidence

ORD record
ord-f8615f63ebaf46ac8be6076ac0084123
Source dataset
uspto-grants-2007_11
Patent number
US07291635B2

Reaction notes

Loading…