4-Methylmorpholine → 6-chloro-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

HRID 1476377Notes

Reaction equation

HRID 1476377 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:14]([OH:16])=O)[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[NH2:17][CH2:18][C:19]1[C:20](=[O:29])[NH:21][C:22]([CH3:28])=[CH:23][C:24]=1[CH2:25][CH2:26][CH3:27].ON1C2N=CC=CC=2N=N1.CN1CCOCC1>C(Cl)CCl.CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:14]([NH:17][CH2:18][C:19]2[C:20](=[O:29])[NH:21][C:22]([CH3:28])=[CH:23][C:24]=2[CH2:25][CH2:26][CH3:27])=[O:16])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:12])[CH3:13])[C:9]=2[CH:10]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 181649HOAt2×HCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetateHCID 674688776-chloro-1-(1-methylethyl)-1H-indazole-4-carboxylic acid

Product 1

HCID 545964886-chloro-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 679Dimethyl SulfoxideSolvent

Procedure

6-chloro-1-(1-methylethyl)-1H-indazole-4-carboxylic acid (0.10 g, 0.419 mmol), 3-(aminomethyl)-6-methyl-4-propyl-2(1H)-pyridinone (0.109 g, 0.503 mmol), 1-hydroxy-7-azabenzotriazole (0.080 g, 0.587 mmol), and then EDC (0.112 g, 0.587 mmol) were added to DMSO (4.0 mL). N-methylmorpholine (0.184 mL, 1.676 mmol) was quickly added via syringe. The contents were stirred at RT overnight Additional HOAT and EDC were added, and the contents were stirred for another 6 h. The contents were slowly poured onto 45 mL of ice-water wherein solid precipitation occurred. The contents were stirred for 10 min., and then allowed to stand for another 10 min. The contents were filtered, the collected solid washed with ca. 5 mL of water. The solid was air dried for 15 min. then dried in vacuum oven at 45° C. for 24 h. The title compound was collected as a white solid (0.160 g, 93% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.89 (t, J=7.33 Hz, 3H) 1.42-1.58 (m, 8H) 2.14 (s, 3H) 2.52-2.58 (m, 1H) 4.36 (d, J=5.05 Hz, 2H) 5.04 (quin, J=6.57 Hz, 1H) 5.91 (s, 1H) 7.59 (d, J=1.52 Hz, 1H) 8.06 (s, 1H) 8.38 (s, 1H) 8.61 (t, J=4.80 Hz, 1H) 11.54 (s, 1H); MS (ES) [M+H]+ 400.9.

Workup

  1. additionwere added
  2. stirringThe contents were stirred for 10 min.
  3. waitto stand for another 10 min
  4. filtrationThe contents were filtered
  5. washthe collected solid washed with ca. 5 mL of water
  6. customdried for 15 min.
  7. customthen dried in vacuum oven at 45° C. for 24 h

Sources & evidence

ORD record
ord-fd2ef06c2e594053804ae350c2d44414
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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