Acetic Acid → HCID 178461132, compound

HRID 1923159Notes

Reaction equation

HRID 1923159 reaction equation
[C:1]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[N:13](C3CCCCO3)[C:14]3[C:19]([N:20]=2)=[C:18]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:17]=[C:16]([NH:27][C:28]2[C:29]([NH2:34])=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:15]=3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[F:41][C:42]([F:47])([CH3:46])[C:43](O)=O.CN(C)C=O.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(O)(=O)C>>[C:1]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[NH:13][C:14]3[C:19]([N:20]=2)=[C:18]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:17]=[C:16]([N:27]2[C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[N:34]=[C:43]2[C:42]([F:47])([F:41])[CH3:46])[N:15]=3)[CH2:7][CH2:6]1)([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 6

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27828252,2-Difluoropropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67492630HCID 67492630, compound

Product 1

HCID 178461132HCID 178461132, compoundYield 18.9%

Conditions

Temperature
0 °C

Procedure

N1-(8-((4-tert-butylpiperazin-1-yl)methyl)-6-morpholino-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-2-yl)benzene-1,2-diamine (0.085 g, 0.15 mmol) and 2,2-difluoropropanoic acid (0.019 g, 0.17 mmol) were dissolved in N,N-dimethylformamide (2 mL, 0.02 mol). N,N-Diisopropylethylamine (0.054 mL, 0.31 mmol) was added. The resulting solution was cooled at 0° C. for 20 minutes. N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.070 g, 0.00018 mol) was added and the reaction stirred overnight at room temperature. The reaction mixture was concentrated to dryness. Acetic acid (3.0 mL, 0.053 mol) was added to the crude residue and the reaction mixture was heated at 90° C. for 18 hours. The reaction mixture was cooled, filtered and concentrated to dryness. The crude was purified by reverse phase HPLC to give 457 (15.3 mg, 18%). [M+H]+=540.3

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. temperaturethe reaction mixture was heated at 90° C. for 18 hours
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe crude was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-5c0fc555ab7e401c9a088b27bf62b819
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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