Methylamine → 1-(4-Bromo-2-fluoro-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3,3-dimethylbutyl)urea

HRID 522742Notes

Reaction equation

HRID 522742 reaction equation
C1C=C(Cl)C=C(C(OO)=O)C=1.[Br:12][C:13]1[C:18]([C:19]2[C:30]([CH3:31])=[N:29][C:22]3[N:23]=[C:24](SC)[N:25]=[CH:26][C:21]=3[CH:20]=2)=[CH:17][C:16]([NH:32][C:33]([NH:35][CH2:36][CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:34])=[C:15]([F:42])[CH:14]=1.[CH3:43][NH2:44].C1COCC1>C(Cl)Cl>[Br:12][C:13]1[C:18]([C:19]2[C:30]([CH3:31])=[N:29][C:22]3[N:23]=[C:24]([NH:44][CH3:43])[N:25]=[CH:26][C:21]=3[CH:20]=2)=[CH:17][C:16]([NH:32][C:33]([NH:35][CH2:36][CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:34])=[C:15]([F:42])[CH:14]=1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 70297m-Chloroperbenzoic acidHCID 898141131-(4-Bromo-2-fluoro-5-(7-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3,3-dimethylbutyl)urea

Product 1

HCID 898137711-(4-Bromo-2-fluoro-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3,3-dimethylbutyl)ureaYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add mCPBA (0.152 g, 0.616 mmol) portion wise to a solution of 1-(4-bromo-2-fluoro-5-(7-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3,3-dimethylbutyl)urea (0.26 g, 0.513 mmol) in DCM (10 mL) and stir at RT for 2 h. Add methylamine in THF (2.0M, 1.027 mL, 2.054 mmol) and stir at RT overnight. Add water, extract with DCM (3×), wash the combined organics with saturated. NaHCO3, then brine, dry over MgSO4, concentrate to dryness and purify via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). Combine fractions, remove the organics under reduced pressure and neutralize the resulting aqueous residue with NaHCO3. Extract the mixture with EtOAc (2×), wash the combined organics with saturated. NaHCO3, then brine, dry over Na2SO4, concentrate to dryness, treat with 1:1 MeCN/H2O, freeze and lyophilize to afford the title compound as a pale yellow solid (34 mg, 13% yield). MS (m/z): 489.1 (M+1)/491.1 (M+3).

Workup

  1. extractionAdd water, extract with DCM (3×)
  2. washwash the combined organics with saturated
  3. dry with materialNaHCO3, then brine, dry over MgSO4
  4. concentrationconcentrate to dryness
  5. custompurify via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
  6. customCombine fractions, remove the organics under reduced pressure
  7. extractionExtract the mixture with EtOAc (2×)
  8. washwash the combined organics with saturated
  9. dry with materialNaHCO3, then brine, dry over Na2SO4
  10. concentrationconcentrate to dryness
  11. additiontreat with 1:1 MeCN/H2O, freeze

Sources & evidence

ORD record
ord-b4d077a68385464d833a8125192cd3b6
Source dataset
uspto-grants-2016_05
Patent number
US09334267B2

Reaction notes

Loading…