3-(6-{[1-(2,2-Difluoro-2H-1,3-benzodioxol-5-yl)cyclopropane-1-carbonyl]amino}-3-methylpyridin-2-yl)benzoic acid--hydrogen chloride (1/1) → Lumacaftor

HRID 242137Notes

Reaction equation

HRID 242137 reaction equation
Cl.[F:2][C:3]1([F:34])[O:7][C:6]2[CH:8]=[CH:9][C:10]([C:12]3([C:15]([NH:17][C:18]4[N:23]=[C:22]([C:24]5[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=5)[C:27]([OH:29])=[O:28])[C:21]([CH3:33])=[CH:20][CH:19]=4)=[O:16])[CH2:14][CH2:13]3)=[CH:11][C:5]=2[O:4]1>O>[F:34][C:3]1([F:2])[O:7][C:6]2[CH:8]=[CH:9][C:10]([C:12]3([C:15]([NH:17][C:18]4[N:23]=[C:22]([C:24]5[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=5)[C:27]([OH:29])=[O:28])[C:21]([CH3:33])=[CH:20][CH:19]=4)=[O:16])[CH2:14][CH2:13]3)=[CH:11][C:5]=2[O:4]1

Participants

3

Reactant 1

HCID 454805183-(6-{[1-(2,2-Difluoro-2H-1,3-benzodioxol-5-yl)cyclopropane-1-carbonyl]amino}-3-methylpyridin-2-yl)benzoic acid--hydrogen chloride (1/1)

Product 1

HCID 16678941LumacaftorYield 98%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A slurry of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid HCl (1 eq) in water (10 vol) is stirred at ambient temperature. A sample is taken after stirring for 24 hours. The sample is filtered and the solid washed with water (2×). The solid sample is submitted for DSC analysis. When DSC analysis indicates complete conversion to Form I, the solid is collected by filtration, washed with water (2×1.0 vol), and partially dried on the filter under vacuum. The solid is dried to constant weight (<1% difference) in a vacuum oven at 60° C. with a slight N2 bleed to afford Form I as an off-white solid (98% yield). 1H NMR (400 MHz, DMSO-d6) 9.14 (s, 1H), 7.99-7.93 (m, 3H), 7.80-7.78 (m, 1H), 7.74-7.72 (m, 1H), 7.60-7.55 (m, 2H), 7.41-7.33 (m, 2H), 2.24 (s, 3H), 1.53-1.51 (m, 2H), 1.19-1.17 (m, 2H).

Workup

  1. filtrationThe sample is filtered
  2. washthe solid washed with water (2×)
  3. filtrationthe solid is collected by filtration
  4. washwashed with water (2×1.0 vol)
  5. custompartially dried on the
  6. filtrationfilter under vacuum
  7. dry with materialThe solid is dried to constant weight (<1% difference) in a vacuum oven at 60° C. with a slight N2

Sources & evidence

ORD record
ord-12c60708dcd646a2b5f2e965a962e1bb
Source dataset
uspto-grants-2014_02
Patent number
US08653103B2

Reaction notes

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