Trifluoroacetic acid methylene chloride → 4-{4-[4-(5-Methyl-tetrazol-1-yl)-phenoxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-piperidine-1-carboxylic acid trifluoro-acetate salt

HRID 1931635Notes

Reaction equation

HRID 1931635 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].ClCCl.C([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([N:24]2[C:28]3=[N:29][CH:30]=[N:31][C:32]([O:33][C:34]4[CH:39]=[CH:38][C:37]([N:40]5[C:44]([CH3:45])=[N:43][N:42]=[N:41]5)=[CH:36][CH:35]=4)=[C:27]3[CH:26]=[N:25]2)[CH2:20][CH2:19]1)=[O:17])(C)(C)C>ClCCl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:45][C:44]1[N:40]([C:37]2[CH:36]=[CH:35][C:34]([O:33][C:32]3[N:31]=[CH:30][N:29]=[C:28]4[N:24]([CH:21]5[CH2:22][CH2:23][N:18]([C:16]([OH:17])=[O:15])[CH2:19][CH2:20]5)[N:25]=[CH:26][C:27]=34)=[CH:39][CH:38]=2)[N:41]=[N:42][N:43]=1

Participants

4

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 445144044-{4-[4-(5-Methyl-tetrazol-1-yl)-phenoxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 669153354-{4-[4-(5-Methyl-tetrazol-1-yl)-phenoxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-piperidine-1-carboxylic acid trifluoro-acetate saltYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 20% trifluoroacetic acid/dichloromethane (12 mL) was added to a solution of 4-{4-[4-(5-methyl-tetrazol-1-yl)-phenoxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (Example 84; 486 mg, 1.02 mmol) in dichloromethane (2 mL) and the mixture was stirred at room temperature for 25 min. The volatiles were evaporated and the residue held at high vacuum and then triturated with ether to give 4-{4-[4-(5-methyl-tetrazol-1-yl)-phenoxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-piperidine-1-carboxylic acid trifluoro-acetate salt (493 mg, 98%) as a white solid. This was taken up in dichloromethane (3 mL) and diisopropylethylamine (243 μL, 1.37 mmol) was added. The mixture was cooled to 0° C., and isopropyl chloroformate (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA; 1 M in toluene; 458 μL, 0.46 mol) was added dropwise. The mixture was stirred at room temperature for 1.5 h. Water (5 mL) was added and the layers were separated. The organic layers was washed with brine, dried (sodium sulfate), filtered, and evaporated. The residue was purified on a Supelco 11 g column, eluting with 6% methanol/dichloromethane to give 4-{4-[4-(5-methyl-tetrazol-1-yl)-phenoxy]-pyrazolo[3,4-d]pyrimidin-1-yl}-piperidine-1-carboxylic acid isopropyl ester (136 mg, 64%) as a white powder. 1H NMR (DMSO-d6) δ 1.20 (d, 6H, J=6.4 Hz), 1.93-2.05 (m, 4H), 2.59 (s, 3H), 2.96-3.14 (m, 2H), 4.04-4.18 (m, 2H), 4.79 (pentet, 1H, J=6.3 Hz), 4.96-5.08 (m, 1H), 7.61-7.64 (m, 2H), 7.79-7.82 (m, 2H), 8.36 (s, 1H), 8.57 (s, 1H).

Workup

  1. customThe volatiles were evaporated
  2. customtriturated with ether

Sources & evidence

ORD record
ord-ffb887241055436ca2b35d5b7498e942
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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