4-Methylmorpholine → HCID 178513629, compound

HRID 1093819Notes

Reaction equation

HRID 1093819 reaction equation
C[N:2]1CCOCC1.[C:8]1([C:14]2[NH:18][N:17]=[C:16]([C:19]([NH:21][CH2:22][C:23]([N:25]3[CH2:30][CH2:29][CH:28]([O:31][C:32]4[CH:40]=[CH:39][CH:38]=[CH:37][C:33]=4[C:34]([OH:36])=O)[CH2:27][CH2:26]3)=[O:24])=[O:20])[CH:15]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.ClC(OCC(C)C)=O>C1COCC1>[C:34]([C:33]1[CH:37]=[CH:38][CH:39]=[CH:40][C:32]=1[O:31][CH:28]1[CH2:27][CH2:26][N:25]([C:23](=[O:24])[CH2:22][NH:21][C:19]([C:16]2[CH:15]=[C:14]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[NH:18][N:17]=2)=[O:20])[CH2:30][CH2:29]1)(=[O:36])[NH2:2]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 178523500HCID 178523500, compound

Product 1

HCID 178513629HCID 178513629, compoundYield 60.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-Methyl morpholine (28 mg, 0.28 mmol) was added to a cold (−70° C.) solution of 2-(1-{2-[(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetyl}-piperidin-4-yloxy)-benzoic acid (100 mg, 0.2 mmol) in THF (2 mL) followed by isobutyl chloroformate (41 mg, 0.3 mmol) and stirring was continued at the at −70° C. for 1 hr. After complete formation of anhydride, ammonia gas was bubbled through the reaction mixture at −70° C. for 10 minutes. The resulting mixture was then stirred at room temperature for 1 hr. Water (10 mL) was added, the precipitated was filtered and dried to afford 54 mg (60.6% yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-carbamoyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 448.18, 93.4%. 1H NMR (300 MHz, DMSO-d6): δ 7.9 (m, 1H), 7.8 (m, 2H), 7.5 (m, 3H), 7.4 (m, 1H), 7.3 (m, 1H), 7.1 (m, 2H), 4.3 (s, 2H), 4.0 (m, 1H), 3.8 (m, 1H), 3.5 (m, 2H), 2.1 (m, 3H), 1.9 (m, 3H), 1.1 (m, 1H).

Workup

  1. customat −70° C.
  2. customfor 1 hr
  3. customAfter complete formation of anhydride, ammonia gas was bubbled through the reaction mixture at −70° C. for 10 minutes
  4. stirringThe resulting mixture was then stirred at room temperature for 1 hr
  5. additionWater (10 mL) was added
  6. filtrationthe precipitated was filtered
  7. customdried

Sources & evidence

ORD record
ord-64100b22567d4a1886db733cdd650a34
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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