Methanesulfonic Acid → HCID 58065431, compound

HRID 1964735Notes

Reaction equation

HRID 1964735 reaction equation
O[C@H:2]([CH3:40])[CH2:3][NH:4][C:5]([C:7]1[NH:8][C:9]([C:12]2[CH:17]=[C:16]([O:18][C:19]3[CH:24]=[N:23][C:22]([C:25]([N:27]4[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]4)=[O:26])=[CH:21]N=3)[CH:15]=[C:14]([O:34][C@@H:35]([CH3:39])[CH2:36][O:37][CH3:38])[CH:13]=2)=[CH:10][CH:11]=1)=[O:6].CS(O)(=O)=O.C(N(CC)CC)C.[Cl-].[NH4+:54]>O1CCCC1>[CH3:38][O:37][CH2:36][C@H:35]([CH3:39])[O:34][C:14]1[CH:15]=[C:16]([CH:17]=[C:12]([C:9]2[NH:8][C:7]([C:5]3[O:6][C@@H:2]([CH3:40])[CH2:3][N:4]=3)=[CH:11][CH:10]=2)[CH:13]=1)[O:18][C:19]1[CH:24]=[N:23][C:22]([C:25]([N:27]2[CH2:28][CH2:29][N:30]([CH3:33])[CH2:31][CH2:32]2)=[O:26])=[CH:21][N:54]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 66890860HCID 66890860, compound

Product 1

HCID 58065431HCID 58065431, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

N-[(2R)-2-Hydroxypropyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-({5-[(4-methylpiperazin-1-yl)carbonyl]pyrazin-2-yl}oxy)phenyl}-1H-pyrrole-2-carboxamide (447 mg, 0.81 mmol) synthesized in Example (131c) was dissolved in tetrahydrofuran (20 mL), and anhydrous methanesulfonic acid (282 mg, 1.62 mmol) and triethylamine (0.34 mL, 2.43 mmol) were added, followed by stirring at 50° C. for 4 hours under nitrogen atmosphere. To the reaction solution, a saturated aqueous ammonium chloride solution (30 mL) was added, and extraction was carried out twice with methylene chloride (30 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: methanol/methylene chloride=0%-5%) to afford the desired compound (279 mg, yield 65%) as a pale yellow solid.

Workup

  1. extractionextraction
  2. washThe organic layer was washed with saturated brine
  3. dry with materialsubsequently dried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe resulting residue was purified
  6. washsilica gel column chromatography (elution solvent: methanol/methylene chloride=0%-5%)

Sources & evidence

ORD record
ord-b3134bd172cf4dd48ace9bf7d89022dc
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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