Water → HCID 86713173, compound

HRID 1500287Notes

Reaction equation

HRID 1500287 reaction equation
[NH2:1][C@H:2]([CH2:21][F:22])[C@@H:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][N:14]=[C:13]([CH2:16][S:17]([CH3:20])(=[O:19])=[O:18])[CH:12]=2)=[CH:7][CH:6]=1)[OH:4].C(N(C(C)C)CC)(C)C.[F:32][CH:33]([F:37])[C:34](Cl)=[O:35].O>CN(C)C=O>[F:32][CH:33]([F:37])[C:34]([NH:1][C@H:2]([CH2:21][F:22])[C@H:3]([OH:4])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][N:14]=[C:13]([CH2:16][S:17]([CH3:20])(=[O:18])=[O:19])[CH:12]=2)=[CH:7][CH:6]=1)=[O:35]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27368902,2-Difluoroacetyl chlorideHCID 86713174HCID 86713174, compound

Product 1

HCID 86713173HCID 86713173, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(1R,2S)-2-amino-3-fluoro-1-(4-(3-(methylsulfonylmethyl)isoxazol-5-yl)phenyl)propan-1-ol (75 mg, 0.21 mmol) in dimethylformamide (2 mL) at 5° C. is treated with diisopropylethylamine (0.055 mL, 0.62 mmol) and then difluoroacetylchloride (0.026 mL, 0.25 mmol) is added and the mixture stirred at room temperature for 1 hour. Water is added (10 mL) and extracted with ethyl acetate (10 mL) and the organics washed with brine (10 mL), dried over MgSO4, filtered, concentrated and purified by reverse phase preparative HPLC to give the title compound (35 mg). 1H NMR (400 MHz, DMSO-d6) δ: 3.10 (s, 3H), 4.33 (m, 1H), 4.40-4.60 (m, 1H), 4.65-4.80 (m, 3H including 2H singlet at 4.75), 4.92 (bs, 1H), 6.17 (t, 1H), 7.08 (s, 1H), 7.51 (d, 2H), 7.86 (d, 2H), 8.80 (d, 1H); m/z (Cl) 407 [M+H].

Workup

  1. extractionextracted with ethyl acetate (10 mL)
  2. washthe organics washed with brine (10 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-1ec75a2e760d42789943953351c1b405
Source dataset
uspto-grants-2015_12
Patent number
US09206126B2

Reaction notes

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