Diisopropylethylamine → HCID 66727008, compound

HRID 1698244Notes

Reaction equation

HRID 1698244 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[N:14][CH:15]=[C:16]([C:17]([OH:19])=O)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:53]([O:60][C:61]([N:63]1[CH2:68][CH2:67][CH:66]([C@@H:69]([NH2:72])[CH2:70][CH3:71])[CH2:65][CH:64]1[C:73](=[O:75])[NH2:74])=[O:62])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1>CN(C=O)C.CCOC(C)=O>[CH2:53]([O:60][C:61]([N:63]1[CH2:68][CH2:67][CH:66]([C@@H:69]([NH:72][C:17]([C:16]2[C:11]3[CH:10]=[N:9][N:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[C:12]=3[CH:13]=[N:14][CH:15]=2)=[O:19])[CH2:70][CH3:71])[CH2:65][CH:64]1[C:73](=[O:75])[NH2:74])=[O:62])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592781371-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acidHCID 66727738HCID 66727738, compound

Product 1

HCID 66727008HCID 66727008, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (360 mg, 1.4 mmol) in DMF (4 mL) was added DIPEA (487 μL, 2.8 mmol). After 10 minutes, HATU (638 mg, 1.68 mmol) was added to the brown solution. After 10 minutes, a solution of 4-((S)-1-amino-propyl)-2-carbamoyl-piperidine-1-carboxylic acid benzyl ester (0.45 g, 1.4 mmol) in DMF (4 mL) and DIPEA (244 μL, 1.4 mmol) was added resulting in a clear solution. After 18 hours, the reaction was diluted with EtOAc (200 mL), washed with NH4Cl (50 mL), water (50 mL), brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography eluting with a gradient of 0-6% MeOH in DCM to afford 2-carbamoyl-4-((S)-1-{[1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]-amino}-propyl)-piperidine-1-carboxylic acid benzyl ester as a light brown foam.

Workup

  1. waitAfter 10 minutes
  2. customresulting in a clear solution
  3. waitAfter 18 hours
  4. washwashed with NH4Cl (50 mL), water (50 mL), brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with a gradient of 0-6% MeOH in DCM

Sources & evidence

ORD record
ord-b4d793d582414fd6b25b2b49ebc696b0
Source dataset
uspto-grants-2012_04
Patent number
US08163918B2

Reaction notes

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