Trifluoroacetic acid → N-((1R,2S)-1-(4-(2-(aminomethyl)thiazol-5-yl)phenyl)-3-fluoro-1-hydroxypropan-2-yl)-2,2-dichloroacetamide

HRID 1487440Notes

Reaction equation

HRID 1487440 reaction equation
[Cl:1][CH:2]([Cl:31])[C:3]([NH:5][C@H:6]([CH2:29][F:30])[C@@H:7]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:19][C:18]([CH2:20][NH:21]C(=O)OC(C)(C)C)=[N:17][CH:16]=2)=[CH:11][CH:10]=1)[OH:8])=[O:4].FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[NH2:21][CH2:20][C:18]1[S:19][C:15]([C:12]2[CH:13]=[CH:14][C:9]([C@@H:7]([OH:8])[C@H:6]([NH:5][C:3](=[O:4])[CH:2]([Cl:1])[Cl:31])[CH2:29][F:30])=[CH:10][CH:11]=2)=[CH:16][N:17]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86695386tert-butyl ((5-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)thiazol-2-yl)methyl)carbamate

Product 1

HCID 86695387N-((1R,2S)-1-(4-(2-(aminomethyl)thiazol-5-yl)phenyl)-3-fluoro-1-hydroxypropan-2-yl)-2,2-dichloroacetamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a stirred solution of the product of Step 1, Example 4 (0.248 g, 0.50 mmol) in CHCl3 (10 mL) is added trifluoroacetic acid (1.1 mL) and stirred the reaction mixture at room temperature for 2 hours. Reaction mixture is concentrated in vacuo and washed the residue with diethyl ether. Residue is dissolved in 10% methanol in CH2Cl2 and evaporated to dryness then dried under vacuum to give the title compound 1H-NMR (400 MHz, DMSO-d6) δ: 4.20-4.22 (m, 1H), 4.28-32 (m, 0.5H), 4.40-4.49 (m, 2.5H), 4.56-4.60 (m, 0.5H), 467-4.71 (m, 0.5H), 4.89 (t, J=3.8 Hz, 1H), 6.02 (d, J=4.28 Hz, 1H), 6.50 (s, 1H), 7.43 (d, J=8.2 Hz, 2H), 7.62 (d, J=8.2 Hz, 2H), 8.28 (s, 1H), 8.48 (bs, 2H), 8.63 (d, J=9 Hz, 1H). m/z (CI) 392 [M−H].

Workup

  1. customReaction mixture
  2. concentrationis concentrated in vacuo
  3. washwashed the residue with diethyl ether
  4. dissolutionResidue is dissolved in 10% methanol in CH2Cl2
  5. customevaporated to dryness
  6. customthen dried under vacuum

Sources & evidence

ORD record
ord-63fd251242c54b55893808dd0abddc48
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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