Trifluoroacetic acid → Baricitinib trifluoroacetate

HRID 1692898Notes

Reaction equation

HRID 1692898 reaction equation
[CH2:1]([S:3]([N:6]1[CH2:9][C:8]([CH2:32][C:33]#[N:34])([N:10]2[CH:14]=[C:13]([C:15]3[C:16]4[CH:23]=[CH:22][N:21](COCC[Si](C)(C)C)[C:17]=4[N:18]=[CH:19][N:20]=3)[CH:12]=[N:11]2)[CH2:7]1)(=[O:5])=[O:4])[CH3:2].[F:35][C:36]([F:41])([F:40])[C:37]([OH:39])=[O:38]>C(Cl)Cl>[F:35][C:36]([F:41])([F:40])[C:37]([OH:39])=[O:38].[CH2:1]([S:3]([N:6]1[CH2:9][C:8]([CH2:32][C:33]#[N:34])([N:10]2[CH:14]=[C:13]([C:15]3[C:16]4[CH:23]=[CH:22][NH:21][C:17]=4[N:18]=[CH:19][N:20]=3)[CH:12]=[N:11]2)[CH2:7]1)(=[O:4])=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 578688652-(1-(Ethylsulfonyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile

Product 1

HCID 66824323Baricitinib trifluoroacetateYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(ethylsulfonyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-ylacetonitrile (0.111 g, 0.22 mmol) in methylene chloride (3 mL) was added trifluoroacetic acid (2 mL) and the solution was stirred for 1.5 hours. The solvents were removed in vacuo and the residue was dissolved in methanol (3 mL) and ethylenediamine (0.1 mL) was added. After stirring for 3 hours, the volume was reduced in vacuo and the product was purified by preparative-HPLC/MS, (SunFire C18 column, eluting with a gradient of MeCN/H2O containing 0.1% TFA) to afford the product as the trifluoroacetic acid salt (50 mg, 47%).

Workup

  1. customThe solvents were removed in vacuo
  2. dissolutionthe residue was dissolved in methanol (3 mL)
  3. additionethylenediamine (0.1 mL) was added
  4. stirringAfter stirring for 3 hours
  5. customthe product was purified by preparative-HPLC/MS, (SunFire C18 column
  6. washeluting with a gradient of MeCN/H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-6b6bd22a1c0145d79b83d2467c806b31
Source dataset
uspto-grants-2012_04
Patent number
US08158616B2

Reaction notes

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