Hydrochloric Acid → HCID 57907475, compound

HRID 243740Notes

Reaction equation

HRID 243740 reaction equation
N[C:2]1[S:3][CH:4]=[C:5]([CH:7]([CH3:46])[C:8]([NH:10][C:11]2[CH:45]=[CH:44][C:14]([CH2:15][C@@H:16]3[CH2:20][CH2:19][C@H:18]([C@H:21]([O:29][Si](C(C)(C)C)(C)C)[C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=4)[N:17]3C(OC(C)(C)C)=O)=[CH:13][CH:12]=2)=[O:9])[N:6]=1.Cl>CO>[F:28][C:24]1[CH:23]=[C:22]([C@@H:21]([OH:29])[C@@H:18]2[NH:17][C@H:16]([CH2:15][C:14]3[CH:13]=[CH:12][C:11]([NH:10][C:8](=[O:9])[CH:7]([C:5]4[N:6]=[CH:2][S:3][CH:4]=4)[CH3:46])=[CH:45][CH:44]=3)[CH2:20][CH2:19]2)[CH:27]=[CH:26][CH:25]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86634925HCID 86634925, compound

Product 1

HCID 57907475HCID 57907475, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 8 mg (0.01 mmol) tert-butyl (2S,5R)-2-(4-{[2-(2-amino-1,3-thiazol-4-yl)propanoyl]amino}benzyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(3-fluorophenyl)methyl]pyrrolidine-1-carboxylate (isomer 2) in 0.20 mL methanol from Step A was added 0.20 mL conc. HCl and the reaction mixture stirred at room temperature for 1 h. Azeotrop with toluene (2×) to remove water. The residue was taken up in acetonitrile/water/MeOH (9:1:1) and purified on the Gilson HPLC eluting with a 0-50% gradient of acetonitrile/water with 0.05% TFA buffer. The fractions containing the product were combined, frozen, and lyophilized to give a white foam (Example 275) (4.3 mg, 79%). m/z (ES) 440 (MH)+.

Workup

  1. customAzeotrop with toluene (2×) to remove water
  2. custompurified on the Gilson HPLC
  3. washeluting with a 0-50% gradient of acetonitrile/water with 0.05% TFA buffer
  4. additionThe fractions containing the product
  5. temperaturefrozen
  6. customto give a white foam (Example 275) (4.3 mg, 79%)

Sources & evidence

ORD record
ord-c668e56f14f4404ba0d250ca976581fe
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Reaction notes

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