Methylamine → HCID 66689927, compound

HRID 337150Notes

Reaction equation

HRID 337150 reaction equation
[CH:1]1([NH:4][C:5](=[O:35])[C:6]2[CH:11]=[C:10]([N:12]3[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[S:28][CH2:29][CH2:30]O)([CH3:21])[CH3:20])[C:13]3=[O:32])[C:9]([CH3:33])=[C:8]([F:34])[CH:7]=2)[CH2:3][CH2:2]1.[CH2:36]([N:38](CC)CC)C.CS(Cl)(=O)=O.CN>C(Cl)Cl.C(O)C>[CH:1]1([NH:4][C:5](=[O:35])[C:6]2[CH:11]=[C:10]([N:12]3[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]([CH3:20])([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[S:28][CH2:29][CH2:30][NH:38][CH3:36])[CH3:21])[C:13]3=[O:32])[C:9]([CH3:33])=[C:8]([F:34])[CH:7]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 66688879HCID 66688879, compound

Product 1

HCID 66689927HCID 66689927, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

N-Cyclopropyl-3-fluoro-5-{3-[(1-{2-[(2-hydroxyethyl)sulfanyl]phenyl}-1-methylethyl)amino]-2-oxopyrazin-1(2H)-yl}-4-methylbenzamide (Example 320g, 0.15 g) was stirred in DCM (20 mL) and cooled to −40° C. before triethylamine (0.046 mL) and methanesulfonyl chloride (0.024 mL) were added. The reaction was warmed to room temperature and methylamine (40% in water) and ethanol (5 mL) were added. The reaction was then stirred for 18 h at 100° C. The reaction was concentrated in vacuo, then purified on SCX resin eluting with methanol (discarded) and flushing with 20% ammonia in methanol. The crude product was purified by preparative HPLC (Phenomenex Gemini column, eluent: 95-5% gradient of aqueous 0.2% aqueous ammonia in acetonitrile). The fractions containing the desired compound were evaporated to dryness to afford the title compound as a solid (3 mg).

Workup

  1. additionwere added
  2. concentrationThe reaction was concentrated in vacuo
  3. custompurified on SCX resin
  4. washeluting with methanol (discarded)
  5. customflushing with 20% ammonia in methanol
  6. customThe crude product was purified by preparative HPLC (Phenomenex Gemini column, eluent: 95-5% gradient of aqueous 0.2% aqueous ammonia in acetonitrile)
  7. additionThe fractions containing the desired compound
  8. customwere evaporated to dryness

Sources & evidence

ORD record
ord-8ec8ae706691469ebd7f2e5f4730b87a
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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