Methanesulfonic Acid → HCID 178505360, compound

HRID 931218Notes

Reaction equation

HRID 931218 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 73.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To (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, 100 g), prepared by the alternative method described in Example 109-A (Step 1 and Step 2), was added acetonitrile (500 mL). The mixture was stirred for 5 min at room temperature before adding methanesulfonic acid (14.38 mL, 219.29 mmol) over a period of 15 sec. The mixture was stirred for 2 h while cooling back to 19° C. The solids were filtered and washed with acetonitrile (250 mL) and dried under nitrogen for 18 h to afford the title compound (86 g, 73% over two steps from Step 2, alternative method for Example 109-A) as a white solid. HPLC retention time: 4.451 min (Method: Same as for Step 1 in the alternative method described for Example 109-A). Chiral HPLC retention time: 3.837 min (Method: Column: OJ-H 4.6×250 mm, 5 μm; S10|(5): acetonitrile+0.1% isopropylamine, 150 bar, 4 mL/min, 40° C., 0-5.5 min: 5-45% S, 5.5-7.5 min: 45% S, 7.51-8 min: 5% S). 1H NMR (400 MHz, DMSO-d6) δ 1.35-2.03 (m, 12H), 2.32 (s, 3H), 2.53-2.65 (m, 1H), 2.91-3.13 (m, 2H), 3.20-3.35 (m, 2H), 3.35-3.55 (m, 2H), 4.20-4.36 (m, 2H), 7.05 (d, 1H), 7.73 (s, 1H), 7.83 (d, 1H), 8.30 (s, 1H).

Workup

  1. stirringThe mixture was stirred for 2 h
  2. temperaturewhile cooling back to 19° C
  3. filtrationThe solids were filtered
  4. washwashed with acetonitrile (250 mL)
  5. customdried under nitrogen for 18 h

Sources & evidence

ORD record
ord-2dd944d0ed374555a10a3940884cdf52
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

Loading…