Trifluoroacetic acid → 2,2-difluoro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(6-((2-methylpropylsulfonamido)methyl)pyridin-3-yl)phenyl)propan-2-yl)acetamide

HRID 525527Notes

Reaction equation

HRID 525527 reaction equation
[NH2:1][CH2:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C@H:15]3[O:19]C(C)(C)[N:17]([C:22](=[O:26])[CH:23]([F:25])[F:24])[C@@H:16]3[CH2:27][F:28])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH2:36]([S:40](Cl)(=[O:42])=[O:41])[CH:37]([CH3:39])[CH3:38].FC(F)(F)C(O)=O>C(Cl)Cl.C1(C)C=CC=CC=1>[F:24][CH:23]([F:25])[C:22]([NH:17][C@H:16]([CH2:27][F:28])[C@H:15]([OH:19])[C:12]1[CH:11]=[CH:10][C:9]([C:6]2[CH:7]=[N:8][C:3]([CH2:2][NH:1][S:40]([CH2:36][CH:37]([CH3:39])[CH3:38])(=[O:42])=[O:41])=[CH:4][CH:5]=2)=[CH:14][CH:13]=1)=[O:26]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 1822361-Propanesulfonyl chloride, 2-methyl-HCID 866954151-((4S,5R)-5-(4-(6-(aminomethyl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-3-yl)-2,2-difluoroethanone

Product 1

HCID 866954162,2-difluoro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(6-((2-methylpropylsulfonamido)methyl)pyridin-3-yl)phenyl)propan-2-yl)acetamideYield 18%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-((4S,5R)-5-(4-(6-(aminomethyl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-3-yl)-2,2-difluoroethanone (80 mg, 0.2 mmol) in CH2Cl2 (15 mL) at 0° C. is added triethylamine (804, 0.5 mmol) followed by isobutylsulfonyl chloride (29 mg, 0.2 mmol). The reaction is stirred at room temperature for 1 hour. Next, trifluoroacetic acid (1 mL) is added and the reaction is stirred at room temperature for an additional 1 hour. Toluene (20 mL) is added and the reaction is concentrated under vacuum. The crude reaction is purified using reverse-phase chromatography, free-based with saturated NaHCO3, extracted with ethylacetate, and concentrated under vacuum to afford the title compound (17 mg). 1H NMR (400 MHz, DMSO-d6) δ: 0.99 (d, 6H), 2.05-2.11 (m, 1H), 2.94 (d, 2H), 4.28-4.36 (m, 3.5H), 4.41-4.45 (m, 0.5H), 4.52-4.58 (m, 0.5H), 4.65-4.68 (m, 0.5H), 4.89 (m, 1H), 5.90 (d, 1H), 6.21 (t, 1H), 7.47 (d, 2H), 7.54 (d, 1H), 7.69-7.74 (m, 3H), 8.12 (dd, 1H), 8.81-8.83 (m, 2H); m/z (Cl) 474 [M+H].

Workup

  1. stirringthe reaction is stirred at room temperature for an additional 1 hour
  2. concentrationthe reaction is concentrated under vacuum
  3. customThe crude reaction
  4. customis purified
  5. extractionfree-based with saturated NaHCO3, extracted with ethylacetate
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b0a00f767b154c5d89f144ef276772bc
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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