Triethylamine → 2,2-Difluoro-N-((1S,2R)-1-fluoromethyl-2-hydroxy-2-{4-[2-(methanesulfonylamino-methyl)-imidazo[1,2-a]pyridin-7-yl]-phenyl}-ethyl)-acetamide

HRID 525559Notes

Reaction equation

HRID 525559 reaction equation
[NH2:1][C@H:2]([CH2:26][F:27])[C@@H:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][N:14]3[CH:17]=[C:18]([CH2:20][NH:21][S:22]([CH3:25])(=[O:24])=[O:23])[N:19]=[C:13]3[CH:12]=2)=[CH:7][CH:6]=1)[OH:4].C(N(CC)CC)C.[F:35][CH:36]([F:42])[C:37](OCC)=[O:38]>CO>[F:35][CH:36]([F:42])[C:37]([NH:1][C@H:2]([CH2:26][F:27])[C@H:3]([OH:4])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][N:14]3[CH:17]=[C:18]([CH2:20][NH:21][S:22]([CH3:25])(=[O:23])=[O:24])[N:19]=[C:13]3[CH:12]=2)=[CH:7][CH:6]=1)=[O:38]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9961Ethyl difluoroacetateHCID 86695443N-{7-[4-((1R,2S)-2-Amino-3-fluoro-1-hydroxy-propyl)-phenyl]-imidazo[1,2-a]pyridin-2-ylmethyl}-methanesulfonamide

Product 1

HCID 866954442,2-Difluoro-N-((1S,2R)-1-fluoromethyl-2-hydroxy-2-{4-[2-(methanesulfonylamino-methyl)-imidazo[1,2-a]pyridin-7-yl]-phenyl}-ethyl)-acetamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution N-{7-[4-((1R,2S)-2-Amino-3-fluoro-1-hydroxy-propyl)-phenyl]imidazo[1,2-a]pyridin-2-ylmethyl}-methane sulfonamide (88 mg, crude) in methanol (1 mL) is added triethyl amine (0.05 mL, 0.346 mmol) followed by addition of ethyl difluoroacetate (0.02 mL, 0.208 mmol) at 0° C. then stirred at room temperature for 20 h. The reaction mixture is concentrated and purified by flash column chromatography eluting in 2.1% MeOH in CH2Cl2 followed by re-purification by preparative TLC to afford 5 mg and which is re-crystallized in

Workup

  1. concentrationThe reaction mixture is concentrated
  2. custompurified by flash column chromatography
  3. washeluting in 2.1% MeOH in CH2Cl2
  4. customfollowed by re-purification by preparative TLC
  5. customto afford 5 mg and which
  6. customis re-crystallized in

Sources & evidence

ORD record
ord-bf632a0316004dc39587dc576e2867d1
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

Loading…