Methanesulfonic Acid → HCID 178505360, compound

HRID 931217Notes

Reaction equation

HRID 931217 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([C:7]2([C:10]3[NH:31][C:13]4=[N:14][C:15]([N:18]5[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([N:26]6[CH2:30][CH2:29][CH2:28][CH2:27]6)=[O:25])[CH2:19]5)=[CH:16][CH:17]=[C:12]4[N:11]=3)[CH2:9][CH2:8]2)[CH:6]=1.[CH3:32][S:33]([OH:36])(=[O:35])=[O:34]>C(#N)C>[CH3:32][S:33]([OH:36])(=[O:35])=[O:34].[Cl:1][C:2]1[CH:3]=[N:4][N:5]([C:7]2([C:10]3[NH:31][C:13]4=[N:14][C:15]([N:18]5[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([N:26]6[CH2:27][CH2:28][CH2:29][CH2:30]6)=[O:25])[CH2:19]5)=[CH:16][CH:17]=[C:12]4[N:11]=3)[CH2:9][CH2:8]2)[CH:6]=1

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 178521019HCID 178521019, compound

Product 1

HCID 178505360HCID 178505360, compoundYield 91.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-(1-(2-(1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (Example 109-A, 56.49 g, 128.4 mmol) in acetonitrile (130 mL) was added methanesulfonic acid (8.33 mL, 128 mmol). The mixture was stirred for 18 h at room temperature. The mixture was filtered and the solids were rinsed with acetonitrile. The solids were collected and dried under high vacuum for 1 h to afford (R)-(1-(2-(1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone methanesulfonate (62.5 g, 90%). 1H NMR (400 MHz, CDCl3) δ 1.65-1.75 (m, 1H), 1.84-2.13 (m, 11H), 2.75-2.85 (m, 1H), 2.87 (s, 3H), 3.28-3.35 (m, 1H), 3.39-3.57 (m, 4H), 3.65-3.72 (m, 1H), 4.02-4.09 (m, 1H), 4.11-4.17 (m, 1H), 6.73-6.82 (m, 1H), 7.55 (s, 1H), 7.76 (s, 1H), 8.13 (d, 1H); MS (ES+) (M+H) 440; UPLC retention time 0.47 min (Method N). mp=212-214° C. Anal. Calculated for C22H26ClN7O.CH4O3S: C, 51.53; H, 5.64; N, 18.29; Cl, 6.61; S, 5.98. Found: C, 51.28; H, 5.65; N, 18.19; Cl, 6.56; S, 5.96.

Workup

  1. filtrationThe mixture was filtered
  2. washthe solids were rinsed with acetonitrile
  3. customThe solids were collected
  4. customdried under high vacuum for 1 h

Sources & evidence

ORD record
ord-51d3ddc54e404ba0b9f10bf74b64cba1
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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