Trifluoroacetic acid → HCID 178449634, compound

HRID 1053624Notes

Reaction equation

HRID 1053624 reaction equation
C([NH:8][C@@:9]([CH3:37])([CH2:35][CH3:36])[C:10]([O:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]([CH2:29][CH:30]2[CH2:33][CH2:32][CH2:31]2)[C:21]([C:23]2[NH:27][N:26]=[C:25]([Cl:28])[CH:24]=2)=[O:22])=[C:15]([F:34])[CH:14]=1)=[O:11])(OC(C)(C)C)=O.[SiH](CC)(CC)CC.C(O)(C(F)(F)F)=O>C(#N)C>[NH2:8][C@@:9]([CH3:37])([CH2:35][CH3:36])[C:10]([O:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]([CH2:29][CH:30]2[CH2:31][CH2:32][CH2:33]2)[C:21]([C:23]2[NH:27][N:26]=[C:25]([Cl:28])[CH:24]=2)=[O:22])=[C:15]([F:34])[CH:14]=1)=[O:11]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 178449817HCID 178449817, compound

Product 1

HCID 178449634HCID 178449634, compoundYield 62.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (S)-4-((3-chloro-N-(cyclobutylmethyl)-1H-pyrazole-5-carboxamido)methyl)-3-fluorophenyl 2-(Boc-amino)-2-methylbutanoate (0.020 g, 0.037 mmol) in ACN 2 mL was added 0.5 mL Et3SiH and 0.5 ml TFA, and then stirred at r.t. for overnight. After removed the solvent, chromatography on silica gel with 0-40% methanol in DCM give the crude product. Then, the crude product was purified one more time by preparative HPLC (Water/ACN, 5-100%, 15 mins, then 100%, 5 mins.) gave pure product (S)-4-((3-chloro-N-(cyclobutylmethyl)-1H-pyrazole-5-carboxamido)methyl)-3-fluorophenyl 2-amino-2-methylbutanoate (0.010 g, 0.023 mmol, 62% yield).

Workup

  1. customAfter removed the solvent, chromatography on silica gel with 0-40% methanol in DCM
  2. customgive the crude product
  3. customThen, the crude product was purified one more time by preparative HPLC (Water/ACN, 5-100%, 15 mins
  4. custom100%, 5 mins

Sources & evidence

ORD record
ord-5ba9a1a034cb4f7abeae6ac93950afe8
Source dataset
uspto-grants-2016_07
Patent number
US09394257B2

Reaction notes

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