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

HRID 525510Notes

Reaction equation

HRID 525510 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][N:16]=2)=[CH:11][CH:10]=1)[OH:8])=[O:4].FC(F)(F)C(O)=O>C(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)=[N:16][N:17]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86695389tert-butyl ((5-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)-1,3,4-thiadiazol-2-yl)methyl)carbamate

Product 1

HCID 86695390N-((1R,2S)-1-(4-(5-(aminomethyl)-1,3,4-thiadiazol-2-yl)phenyl)-3-fluoro-1-hydroxypropan-2-yl)-2,2-dichloroacetamideYield 135.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl ((5-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)-1,3,4-thiadiazol-2-yl)methyl)carbamate (100 mg, 0.203 mmol) in CH2Cl2 (10 mL) is added trifluoroacetic acid (1.0 mL). After 2 hours the reaction mixture is concentrated in vacuo and the residue washed with diethyl ether. The residue is dissolved in 10% methanol in CH2Cl2 and evaporated to dryness, washed with n-pentane, dried under vacuum to give the title compound (108 mg): 1H-NMR (400 MHz, DMSO-d6) δ 4.27-4.28 (m, 1H), 4.31-4.35 (m, 0.5H), 4.43-4.47 (m, 0.5H), 4.59-4.61 (m, 0.5H), 4.64 (s, 2H), 4.70-4.74 (m, 0.5H), 4.96 (t, J=2.76 Hz, 1H), 6.10 (d, J=4.28 Hz, 1H), 6.48 (s, 1H), 7.54 (d, J=8.32 Hz, 2H), 7.94 (d, J=8.32 Hz, 2H), 8.60 (bs, 2H), 8.64 (d, J=9.12 Hz, 1H). LC-Ms (m/z): [M+H]=393.10.

Workup

  1. concentrationAfter 2 hours the reaction mixture is concentrated in vacuo
  2. washthe residue washed with diethyl ether
  3. dissolutionThe residue is dissolved in 10% methanol in CH2Cl2
  4. customevaporated to dryness
  5. washwashed with n-pentane
  6. customdried under vacuum

Sources & evidence

ORD record
ord-2ecffe7f2c4f4de98dc4dd5fb88df89c
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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