Sodium Carbonate → N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 1521333Notes

Reaction equation

HRID 1521333 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[NH:11][C:12]([C:14]1[N:18]2[CH:19]=[CH:20][C:21]([C:23]3[N:24]([CH3:28])[N:25]=[CH:26][CH:27]=3)=[CH:22][C:17]2=[N:16][CH:15]=1)=[O:13].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH3:51][C@H:52]1[CH2:57][CH2:56][CH2:55][C@@H:54]([CH3:58])[N:53]1[CH2:59][CH2:60][NH2:61].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O>[CH3:51][C@H:52]1[CH2:57][CH2:56][CH2:55][C@@H:54]([CH3:58])[N:53]1[CH2:59][CH2:60][NH:61][C:6]([C:5]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([NH:11][C:12]([C:14]2[N:18]3[CH:19]=[CH:20][C:21]([C:23]4[N:24]([CH3:28])[N:25]=[CH:26][CH:27]=4)=[CH:22][C:17]3=[N:16][CH:15]=2)=[O:13])[CH:4]=1)=[O:8]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 757711-HydroxybenzotriazoleHCID 7837022-(cis-2,6-Dimethyl-1-piperidinyl)ethanamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 712829094-fluoro-3-(7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamido)benzoic acid

Product 1

HCID 71283030N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

4-Fluoro-3-{[7-(2-methyl-2H-pyrazol-3-yl)-imidazo[1,2-a]pyridine-3-carbonyl]amino}-benzoic acid (step 2) (450 g, 1.19 mol), EDC.HCl (454.8 g, 2.372 mol) and HOBt (181.6 g, 1.186 mol) in DMF (3.2 L) at 25° C. were stirred for 1.5 hr. The reaction was monitored by HPLC. To the reaction mixture was dropwise added cis 2-(2,6-dimethyl-piperidin-1-yl)-ethylamine (222.5 g, 1.423 mol) over 10 min and stirring continued for 30 min. To the reaction mixture was dropwise an aqueous solution of Na2CO3 (5%, 6 L) over 120 min and the resulting solid was collected by filtration and washed with water (5 L). To the solid was added ethanol (5 L) followed by heating to 70° C. to obtain a clear solution. Water (1. 5 L) was dropwise added at 70° C. and stirred for 30 min. The clear solution was slowly cooled to 25° C. over 2 hr. The solid was filtered, washed with ethanol (500 mL) and dried under vacuum at 50° C. overnight to afford the title compound as a white solid;

Workup

  1. customover 10 min
  2. customover 120 min
  3. filtrationthe resulting solid was collected by filtration
  4. washwashed with water (5 L)
  5. additionTo the solid was added ethanol (5 L)
  6. customto obtain a clear solution
  7. stirringstirred for 30 min
  8. temperatureThe clear solution was slowly cooled to 25° C. over 2 hr
  9. filtrationThe solid was filtered
  10. washwashed with ethanol (500 mL)
  11. customdried under vacuum at 50° C. overnight

Sources & evidence

ORD record
ord-829089bc7f9f46ad8d60218711bf33db
Source dataset
uspto-grants-2015_07
Patent number
US09073921B2

Reaction notes

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