Trifluoroacetic acid → Ethyl 3-methyl-3-[4-(1h-pyrrolo[2,3-b]pyridin-4-yl)-1h-pyrazol-1-yl]butanoate trifluoroacetate salt

HRID 40888Notes

Reaction equation

HRID 40888 reaction equation
[CH3:1][C:2]([N:10]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]3[N:21](COCC[Si](C)(C)C)[CH:22]=[CH:23][C:16]=23)[CH:12]=[N:11]1)([CH3:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[C:32]([OH:38])([C:34]([F:37])([F:36])[F:35])=[O:33]>>[F:35][C:34]([F:37])([F:36])[C:32]([OH:38])=[O:33].[CH3:9][C:2]([N:10]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]3[NH:21][CH:22]=[CH:23][C:16]=23)[CH:12]=[N:11]1)([CH3:1])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57477580ethyl 3-methyl-3-[4-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]butanoate

Product 1

HCID 66597778Ethyl 3-methyl-3-[4-(1h-pyrrolo[2,3-b]pyridin-4-yl)-1h-pyrazol-1-yl]butanoate trifluoroacetate saltYield 26%

Procedure

Ethyl 3-methyl-3-[4-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]butanoate (20 mg, 0.0000452 mol) was stirred in 1 mL TFA for 1 hour. Then excess TFA was removed in vacuo. The residue was stirred for 16 hours in 2 mL MeOH containing 0.5 mL NH4OH. Evaporation of the volatiles was followed by purification by preparative-HPLC (C18 eluting with a gradient of ACN/H2O containing 0.1% TFA) to afford ethyl 3-methyl-3-[4-(1H-pyrrolo[2,3-b]-pyridin-4-yl)-1H-pyrazol-1-yl]butanoate, trifluoroacetate salt (5 mg, 26%). 1H NMR (400 MHz, d6-DMSO): δ □12.19 (s, 1H), 8.61 (br s, 1H), 8.34-8.22 (br m, 2H), 7.62 (br s, 1H), 7.51 (br d, 1H), 7.02 (br s, 1H), 3.91 (q, 2H), 2.96 (s, 2H), 1.70 (s, 6H), 1.02 (t, 3H); MS (ES): 313 (M+1).

Workup

  1. customThen excess TFA was removed in vacuo
  2. customEvaporation of the volatiles
  3. customwas followed by purification by preparative-HPLC (
  4. washC18 eluting with a gradient of ACN/H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-11d62a019e8348f0821b18ca4bd82cbd
Source dataset
uspto-grants-2013_09
Patent number
US08530485B2

Reaction notes

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