Ethyl Acetate → HCID 71115218, compound

HRID 1502480Notes

Reaction equation

HRID 1502480 reaction equation
[F:1][C@@H:2]1[CH2:4][C@@H:3]1[C:5]([OH:7])=O.CN(C(O[N:16]1N=N[C:18]2[CH:19]=[CH:20][CH:21]=[N:22][C:17]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([N:35]([CH2:39][CH3:40])[CH:36]([CH3:38])C)(C)C.C(O[CH2:45][CH3:46])(=O)C>CN(C=O)C>[F:1][C@@H:2]1[CH2:4][C@@H:3]1[C:5]([NH:16][C:17]1[N:22]=[CH:21][C:20]2[C:19]([CH:18]=1)=[CH:17][N:22]=[C:21]([C:40]1[CH:39]=[N:35][CH:36]=[CH:38][C:45]=1[CH3:46])[CH:20]=2)=[O:7]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10011855(1R,2R)-2-fluorocyclopropanecarboxylic acid

Product 1

HCID 71115218HCID 71115218, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (1R,2R)-2-fluorocyclopropanecarboxylic acid (35 mg, 0.34 mmol), HATU (139 mg, 0.36 mmol), and N,N-diisopropylethylamine (89 mg, 0.68 mmol) in DMF (1 mL) was heated at 70° C. for 8 hours. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (25 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by reverse phase HPLC purification (5-85% ACN in water w/0.1% NH4OH, 14 min). Desired fractions were combined and evaporated in vacuo to afford the title compound as an off-white solid (25 mg, 46%). 1H NMR (400 MHz, DMSO) δ 11.20 (s, 1H), 9.50 (s, 1H), 9.34 (s, 1H), 8.68 (s, 1H), 8.68 (s, 1H), 8.50 (d, J=5.0 Hz, 1H), 8.19 (s, 1H), 7.39 (d, J=5.0 Hz, 1H), 5.08-4.85 (m, 1H), 2.44 (s, 3H), 2.30 (m, 1H), 1.72 (m, 1H), 1.23 (m, 1H). LCMS (Method E): RT=3.166 min, M+H+=323.2.

Workup

  1. washwashed with water (25 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue that
  7. customwas purified by reverse phase HPLC purification (5-85% ACN in water w/0.1% NH4OH, 14 min)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-2ce9b4c3a88440998429ca082ad5a0b4
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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