Trifluoroacetic acid → HCID 57525637, compound

HRID 1594403Notes

Reaction equation

HRID 1594403 reaction equation
[C:1]([N:5]1[C:9]([NH2:10])=[CH:8][C:7]([CH:11]2[CH2:14][C:13]([O:17][CH3:18])([O:15][CH3:16])[CH2:12]2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:26](O)([C:28]([F:31])([F:30])[F:29])=[O:27].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>CCOC(C)=O>[C:1]([N:5]1[C:9]([NH:10][C:26](=[O:27])[C:28]([F:31])([F:30])[F:29])=[CH:8][C:7]([CH:11]2[CH2:12][C:13]([O:15][CH3:16])([O:17][CH3:18])[CH2:14]2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 57525626HCID 57525626, compound

Product 1

HCID 57525637HCID 57525637, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirring solution of 2-tert-butyl-5-(3,3-dimethoxy-cyclobutyl)-2H-pyrazol-3-ylamine (5.0 g, 19.7 mmol) in EtOAc (40 mL) was added triethylamine (27 mL, 197 mmol), TFA (2.3 mL, 29.6 mmol), followed by a solution of 1-propanephosphonic acid cyclic anhydride (25 mL, 50 wt % sol. in EtOAc, 39.4 mmol). After 72 hr, the reaction was diluted with EtOAc and washed with aqueous NaOH (1 N). The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of this material was accomplished by MPLC, using a Biotage® column (35 L), eluting with 25% EtOAc/hexanes. The product-containing fractions were collected and concentrated to yield the title compound (4.1 g, 60% yield) as a colorless oil. 400 MHz 1H NMR (CDCl3) d 8.00 (bs, 1H), 6.26 (s, 1H), 3.22 (dddd, J=8.7, 8.7, 8.7, 8.7, Hz, 1H), 3.18 (s, 3H), 3.15 (s, 3H), 2.61-2.55 (m, 2H), 2.25-2.19 (m, 2H), 1.59 (s, 9H). LRMS m/z (APCI+) 350 (M+1).

Workup

  1. washwashed with aqueous NaOH (1 N)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification of this material
  6. washeluting with 25% EtOAc/hexanes
  7. customThe product-containing fractions were collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-915751c0add54f78a2a02dc66c6370a3
Source dataset
uspto-grants-2007_11
Patent number
US07300944B2

Reaction notes

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