Pyridine → 5-Fluoro-2-methyl-N-[2-methyl-6-((2S,3'R)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl]-benzamide

HRID 536317

Reaction equation

HRID 536317 reaction equation
[CH3:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([N:9]2[CH2:13][CH2:12][C@@H:11]([N:14]3[CH2:18][CH2:17][CH2:16][C@@H:15]3[CH3:19])[CH2:10]2)[N:3]=1.N1C=CC=CC=1.[F:26][C:27]1[CH:28]=[CH:29][C:30]([CH3:36])=[C:31]([CH:35]=1)[C:32](Cl)=[O:33].C(O)C(N)(CO)CO>ClCCCl>[F:26][C:27]1[CH:28]=[CH:29][C:30]([CH3:36])=[C:31]([CH:35]=1)[C:32]([NH:8][C:7]1[C:2]([CH3:1])=[N:3][C:4]([N:9]2[CH2:13][CH2:12][C@@H:11]([N:14]3[CH2:18][CH2:17][CH2:16][C@@H:15]3[CH3:19])[CH2:10]2)=[CH:5][CH:6]=1)=[O:33]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6503Tris(hydroxymethyl)aminomethaneHCID 27373835-Fluoro-2-methylbenzoyl chlorideHCID 674804612-methyl-6-[(3R)-3-[(2S)-2-methylpyrrolidin-1-yl]pyrrolidin-1-yl]pyridin-3-amine

Product 1

HCID 545971545-Fluoro-2-methyl-N-[2-methyl-6-((2S,3'R)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl]-benzamideYield 29.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

To a solution of 2-methyl-6-[(3R)-3-[(2S)-2-methylpyrrolidin-1-yl]pyrrolidin-1-yl]pyridin-3-amine (22.7 mg, 0.09 mmol) in DCE (1 mL) was added pyridine (0.22 mL, 2.7 mmol) followed by a solution of 5-fluoro-2-methyl-benzoyl chloride (47 mg, 0.27 mmol) in DCE (1 mL) and stirred at ambient temperature for 5 hours. To this mixture was then added trisamine resin (200 mg, 0.8 mmol, 4 mmol/g loading), stirred for 30 min, filtered and concentrated to afford a crude solid which was purified by flash column chromatography (5% 7N NH3 in MeOH/CH2Cl2) to obtain 10.4 mg of the title compound.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated
  3. customto afford a crude solid which
  4. customwas purified by flash column chromatography (5% 7N NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-8697713b200448d6955af2e1e66e2c71
Source dataset
uspto-grants-2014_10
Patent number
US08859588B2

Linked notes

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