Trifluoroacetic acid → HCID 66672664, compound

HRID 2091648Notes

Reaction equation

HRID 2091648 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C@H:10]1[NH:18][C:17]2[C:12](=[N:13][C:14]([NH:19][CH:20]3[CH2:29][CH2:28][C:23]4(OCC[O:24]4)[CH2:22][CH2:21]3)=[N:15][CH:16]=2)[N:11]1[CH:30]1[CH2:35][CH2:34][CH:33]([OH:36])[CH2:32][CH2:31]1.FC(F)(F)C(O)=O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C@H:10]1[NH:18][C:17]2[C:12](=[N:13][C:14]([NH:19][CH:20]3[CH2:21][CH2:22][C:23](=[O:24])[CH2:28][CH2:29]3)=[N:15][CH:16]=2)[N:11]1[CH:30]1[CH2:35][CH2:34][CH:33]([OH:36])[CH2:32][CH2:31]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66672368HCID 66672368, compound

Product 1

HCID 66672664HCID 66672664, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-[(R)-8-(2,4-Difluoro-phenylamino)-2-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-7H-purin-9-yl]-cyclohexanol (0.62 g, 1.7 mmol) was dissolved in 25 mL of methylene chloride under an N2 atmosphere. Trifluoroacetic acid (5 mL) was then added dropwise via addition funnel. After stirring for 24 h the resulting reaction mixture was concentrated under reduced pressure. Saturated sodium bicarbonate was added to the resulting residue until pH 12. The basic aqueous layer was then extracted using chloroform (2×75 mL). The combined organic layers were dried with MgSO4. The crude product was then purified on the preparatory HPLC using a 5-70% CH3CN/H2O over 39 minutes method. Fractions of greater then 98% purity via analytical HPLC were combined and concentrated. Excess trifluoroacetic acid was removed by washing the product with 1.75 M potassium carbonate (3×100 mL). The organic layers were then concentrated to dryness under vacuum to give the ketone (0.015 g 0.033 mmol, 12%) as a fine white powder: LC-MS (m/z) 457.1 [M+1]+.

Workup

  1. customthe resulting reaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. additionSaturated sodium bicarbonate was added to the resulting residue until pH 12
  4. extractionThe basic aqueous layer was then extracted
  5. dry with materialThe combined organic layers were dried with MgSO4
  6. customThe crude product was then purified on the preparatory HPLC
  7. customover 39 minutes
  8. concentrationconcentrated
  9. customExcess trifluoroacetic acid was removed
  10. washby washing the product with 1.75 M potassium carbonate (3×100 mL)
  11. concentrationThe organic layers were then concentrated to dryness under vacuum

Sources & evidence

ORD record
ord-62824c949cd442828fe3ed1946c27e28
Source dataset
uspto-grants-2013_05
Patent number
US08440661B2

Reaction notes

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