Trifluoroacetic acid → HCID 86677785, compound

HRID 1499862Notes

Reaction equation

HRID 1499862 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:15]([O:34][CH2:35][CH3:36])=[C:16]([CH:23]4[CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24]4)[C:17]([C:21]#[N:22])=[C:18]([Cl:20])[CH:19]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.FC(F)(F)C(O)=O>C(Cl)Cl.CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[CH:19]=[C:18]([Cl:20])[C:17]([C:21]#[N:22])=[C:16]([CH:23]4[CH2:24][NH:25][CH2:26]4)[C:15]=3[O:34][CH2:35][CH3:36])[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86677786HCID 86677786, compound

Product 1

HCID 86677785HCID 86677785, compoundYield 104.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-cyano-2-ethoxyphenyl}azetidine-1-carboxylate (peak 1 enantiomer from step 5) (2.2 g, 4.2 mmol) in methylene chloride (11 mL) was treated with trifluoroacetic acid (11 mL) dropwise and stirred at room temperature for 30 min. The reaction mixture was concentrated to an oil that was reconcentrated from ethanol (2×) to give a residue. This material was dissolved in a minimum amount of methanol, added dropwise to ice cooled saturated sodium bicarbonate solution (100 ml), and extracted several times with 2:1 dichloromethane/isopropanol to give the desired product (1.8 g, quantitative) that was used without further purification. A small amount of the desired product was purified by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product. The product was isolated as a single enantiomer. 1H NMR (400 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.47 (s, 1H), 6.23 (q, J=7.0 Hz, 1H), 4.37-4.26 (m, 1H), 3.91-3.61 (m, 6H), 2.54 (s, 3H), 1.71 (d, J=7.1 Hz, 3H), 1.32 (t, J=7.0 Hz, 3H). LCMS for C20H23ClN7O (M+H)+: m/z=412.2; Found: 412.1.

Workup

  1. concentrationThe reaction mixture was concentrated to an oil that
  2. customto give a residue
  3. extractionextracted several times with 2:1 dichloromethane/isopropanol

Sources & evidence

ORD record
ord-81c7393e6a1d4b73982e58f8dbe7f861
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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