tert-Butyldimethylsilane → HCID 58997411, compound

HRID 1591990Notes

Reaction equation

HRID 1591990 reaction equation
[C:1]([NH:4][C@@H:5]([CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:6]([NH:8][C@@H:9]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][N:26]2[CH2:30][C:29](=[O:31])[N:28](CC3C=CC(OC)=CC=3)[S:27]2(=[O:42])=[O:41])[CH:20]=1)[C:10]([NH:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[O:11])=[O:7])(=[O:3])[CH3:2].C([SiH](C)C)(C)(C)C>C(O)(C(F)(F)F)=O>[C:1]([NH:4][C@@H:5]([CH2:43][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[C:6]([NH:8][C@H:9]([C:10](=[O:11])[NH:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][N:26]2[CH2:30][C:29](=[O:31])[NH:28][S:27]2(=[O:42])=[O:41])[CH:20]=1)=[O:7])(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 5072427tert-ButyldimethylsilaneHCID 67139620HCID 67139620, compound

Product 1

HCID 58997411HCID 58997411, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

The title H compound, (S)-2-((S)-2-acetylamino-3-phenyl-propionylamino)-3-{3-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-ylmethyl]-phenyl}-N-pentyl-propionamide (77 mg, 0.111 mmol) is dissolved in TFA (2.2 mL) containing t-butyl-dimethylsilane (0.055 mL, 0.33 mmol) and heated at 80° C. for 3.75 h. The reaction is concentrated under nitrogen stream and the resulting tan solid is taken up in 60% MeCN in water. Water (1 mL) is added, and the mixture is filtered through a 0.1 micron Acrodisc filter. 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 7 aliquots and eluted at 30 mL/min with a gradient of 90:10 (water containing 0.1% TFA: 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 the product still containing an unknown impurity by HPLC. This is chromatographed again, using the same column, but a different elution gradient, 90:10 (0.1% TFA in water: MeCN) to 40:60 over 14 min. Fractions containing product are combined and concentrated to yield (S)-2-acetylamino-N-{(S)-1-pentylcarbamoyl-2-[3-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-ylmethyl)-phenyl]-ethyl}-3-phenyl-propionamide as a white film: [M+1]+=572.

Workup

  1. concentrationThe reaction is concentrated under nitrogen stream
  2. additionWater (1 mL) is added
  3. filtrationthe mixture is filtered through a 0.1 micron Acrodisc
  4. filtrationfilter
  5. washeluted at 30 mL/min with a gradient of 90:10 (water containing 0.1% TFA: MeCN) to 10:90 over 5 min
  6. additionFractions containing product
  7. concentrationconcentrated on a Savant Speedvac
  8. customto yield the product
  9. additionstill containing an unknown impurity by HPLC
  10. customThis is chromatographed again
  11. waita different elution gradient, 90:10 (0.1% TFA in water: MeCN) to 40:60 over 14 min
  12. additionFractions containing product
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-0df9c98eef464e4facd2ecdf237a9cca
Source dataset
uspto-grants-2007_11
Patent number
US07291635B2

Reaction notes

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