4-Methylmorpholine → 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1H-indazole-4-carboxamide

HRID 1476425Notes

Reaction equation

HRID 1476425 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:16]([OH:18])=O)[C:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.Cl.[NH2:20][CH2:21][C:22]1[C:23](=[O:30])[NH:24][C:25]([CH3:29])=[CH:26][C:27]=1[CH3:28].Cl.CN(C)CCCN=C=NCC.O.N1C2C(=NC=CC=2)N(O)N=1.CN1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>CS(C)=O.O>[Br:1][C:2]1[CH:3]=[C:4]([C:16]([NH:20][CH2:21][C:22]2[C:23](=[O:30])[NH:24][C:25]([CH3:29])=[CH:26][C:27]=2[CH3:28])=[O:18])[C:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:12][CH2:13][CH2:14][CH2:15]3)[C:9]=2[CH:10]=1

Participants

9

Reactant 6

HCID 79724-MethylmorpholineHCID 10340Sodium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219174661-Hydroxy-7-azabenzotriazol hydrateHCID 438104513-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one hydrochlorideHCID 674684486-bromo-1-cyclopentyl-1H-indazole-4-carboxylic acid

Product 1

HCID 545970746-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1H-indazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

6-bromo-1-cyclopentyl-1H-indazole-4-carboxylic acid (1.44 g, 4.61 mmol), 3-(aminomethyl)-4,6-dimethyl-2(1H)-pyridinone hydrochloride (1.138 g, 6.03 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (1.335 g, 6.96 mmol), and 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol hydrate (1.073 g, 6.96 mmol) were suspended in DMSO (8.00 mL), followed by N-methylmorpholine (2.82 g, 27.8 mmol). The reaction mixture was stirred at room temperature overnight to afford a slurry. The slurry was diluted with DMSO (10 mL) and added dropwise to a ice-chilled aqueous solution of 1N Na2CO3 (50 ml) and water (200 mL), and stirred rapidly for 30 min. The precipitate was collected by vacuum filtration and washed with water. The cake was dried in the vacuum oven at 60° C. overnight (16 h). The title compound was obtained as a pale yellow-white solid (2.05 g, 98% yield). 1H NMR (400 MHz, DMSO-δ6) δ 11.50 (br. s., 1H), 8.64 (br. s., 1H), 8.37 (s, 1H), 8.20 (s, 1H), 7.70 (d, J=1.52 Hz, 1H), 5.89 (s, 1H), 5.22 (quin, J=7.01 Hz, 1H), 4.34 (d, J=4.55 Hz, 2H), 2.20 (s, 3H), 2.13 (s, 3H), 2.06-2.11 (m, 2H), 1.91-2.03 (m, 2H), 1.80-1.91 (m, 2H), 1.61-1.75 (m, 2H). LC-MS (ES) [M+H]+ 443.0.

Workup

  1. customto afford a slurry
  2. stirringstirred rapidly for 30 min
  3. filtrationThe precipitate was collected by vacuum filtration
  4. washwashed with water
  5. customThe cake was dried in the vacuum oven at 60° C. overnight (16 h)

Sources & evidence

ORD record
ord-c5e689a6a65b4fbfbb194ecc4fd93f62
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

Loading…