Triethylamine → 3-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxamide

HRID 595324Notes

Reaction equation

HRID 595324 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:15]2[CH:16]=[N:17][N:18]([CH:20]3[CH2:23][CH:22]([C:24](O)=[O:25])[CH2:21]3)[CH:19]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:7]=1.C([N:29](CC)CC)C.[OH-].[NH4+]>CN(C=O)C.C(OCC)(=O)C.O.CO.ClCCl>[CH3:1][C:2]1[CH:3]=[C:4]([C:15]2[CH:16]=[N:17][N:18]([CH:20]3[CH2:21][CH:22]([C:24]([NH2:29])=[O:25])[CH2:23]3)[CH:19]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:10]=[CH:11][CH:12]=[CH:13][N:14]=2)[CH:7]=1

Participants

9

Reactant 3

HCID 8471TriethylamineHCID 14923Ammonium HydroxideHCID 1182088123-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxylic acid

Product 1

HCID 1182088653-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxamide

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxylic acid (Isomer 1) (170 mg, 0.49 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (187 mg, 0.584 mmol), and triethylamine (0.136 mL, 0.973 mmol) in DMF (5.0 mL) was stirred for 10 minutes, after which time ammonium hydroxide (0.20 mL, 1.46 mmol) was added. The reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was diluted with ethyl acetate (100 mL) and water (10 mL). The organic layer was separated and washed with water (2×10 mL) followed by brine (10 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to afford the crude product residue. The crude product residue was dissolved in a mixture of methanol (6 mL) and dichloromethane (20 mL). The mixture was diluted by the dropwise addition of hexanes (50 mL). The resulting suspension was stirred for 4 hours. The suspension was filtered and the collected solids were washed with hexanes/dichloromethane (1:1, 3×10 mL) followed by neat hexanes (2×10 mL). The collected solids were dried under reduced pressure to afford 3-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxamide (Isomer 1) MS ESI calcd. for C19H21N6O [M+H]+ 349. found 349. 1H NMR (500 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.46 (d, J=4.5 Hz, 2H), 8.15 (s, 1H), 7.78 (s, 1H), 7.72 (s, 1H), 7.40 (s, 1H), 7.37 (s, 1H), 6.98 (s, 1H), 6.88 (s, 1H), 6.81 (t, J=5.0 Hz, 1H), 5.03-4.96 (m, 1H), 3.05-2.98 (m, 1H), 2.69-2.61 (m, 2H), 2.57-2.51 (m, 2H), 2.27 (s, 3H).

Workup

  1. customThe organic layer was separated
  2. washwashed with water (2×10 mL)
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude product residue
  7. stirringThe resulting suspension was stirred for 4 hours
  8. filtrationThe suspension was filtered
  9. washthe collected solids were washed with hexanes/dichloromethane (1:1, 3×10 mL)
  10. customThe collected solids were dried under reduced pressure

Sources & evidence

ORD record
ord-407d81bb340e4c4790388374cde32011
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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