Trifluoroacetic acid → (S)-N-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-2-(2-(5-(hydroxymethyl)thiazol-2-ylamino)acetamido)propanamide

HRID 1755438Notes

Reaction equation

HRID 1755438 reaction equation
[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13](=[O:28])[C@@H:14]([NH:16][C:17](=[O:27])[CH2:18][NH:19][C:20]1[S:21][C:22]([CH:25]=[O:26])=[CH:23][N:24]=1)[CH3:15])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.[BH4-].[Na+].COC.C(O)(C(F)(F)F)=O>CCO.O.[NH4+].[Cl-]>[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13](=[O:28])[C@@H:14]([NH:16][C:17](=[O:27])[CH2:18][NH:19][C:20]1[S:21][C:22]([CH2:25][OH:26])=[CH:23][N:24]=1)[CH3:15])[CH2:4][C:5]1[CH:6]=[CH:7][C:8]([OH:11])=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8254Dimethyl EtherHCID 4311764Sodium borohydrideHCID 86700086(S)-N-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-2-(2-(5-formylthiazol-2-ylamino)acetamido)propanamide

Product 1

HCID 86700087(S)-N-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-2-(2-(5-(hydroxymethyl)thiazol-2-ylamino)acetamido)propanamide

Reagents, catalysts & solvents 2

HCID 25517Ammonium ChlorideSolventHCID 19096565Water ethanolSolvent

Procedure

To a suspension of material from Example 4 (26.7 mg, 0.050 mmol) in a mixture of EtOH/Water (4:1) (3 mL) is added sodium borohydride (18.4 mg, 0.486 mmol) in 3 portions over M5 min. The resulting pale white suspension is allowed to stir at room temp for 3 h. The reaction is diluted with EtOAC (75 mL) and saturated aqueous NH4Cl (12 mL). The water layer is back extracted with EtOAc (6×20 mL), the organic layers were combined, extracted with water (2×10 mL), brine (1×10 mL), dried over Na2SO4, filtered and evaporated to dryness. The aqueous layers were combined, evaporated to dryness, and purified by preparative HPLC (Condition A) using a PHENOMENEX® Luna Axia 30×100 mm S10 column from 5% Solvent B to 45% Solvent B over 10 min, ret. T=4.12 min. The fractions containing the desired product were evaporated to dryness to give 7.3 mg (35%) of a 1:1 mixture of the title compound and its methyl ether as a colorless film as a TFA salt. LC/MS (Condition A): ret. T=0.8 min, (M+Na) 424.12 and ret. T=1.49 min, (M+Na) 444.12.

Workup

  1. extractionThe water layer is back extracted with EtOAc (6×20 mL)
  2. extractionextracted with water (2×10 mL), brine (1×10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customevaporated to dryness
  7. custompurified by preparative HPLC (Condition A)
  8. customover 10 min
  9. customT=4.12 min
  10. additionThe fractions containing the desired product
  11. customwere evaporated to dryness
  12. customto give

Sources & evidence

ORD record
ord-053c2fcbd32a43ba800a15b29f2d4153
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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