Methylamine → HCID 121393767, compound

HRID 1480028Notes

Reaction equation

HRID 1480028 reaction equation
[C:1](N1C=CN=C1)([N:3]1C=CN=C1)=O.[C:13]([C:15]1[CH:20]=[CH:19][C:18]([N:21]2[C:25]([C:26]3[N:30]([CH2:31][C:32](O)=[O:33])[C:29](=[O:35])[N:28]([C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:44])[F:43])[CH:37]=4)[C:27]=3[CH3:46])=[CH:24][CH:23]=[N:22]2)=[CH:17][CH:16]=1)#[N:14].CN>C1COCC1>[C:13]([C:15]1[CH:16]=[CH:17][C:18]([N:21]2[C:25]([C:26]3[N:30]([CH2:31][C:32]([NH:3][CH3:1])=[O:33])[C:29](=[O:35])[N:28]([C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:44])([F:45])[F:43])[CH:37]=4)[C:27]=3[CH3:46])=[CH:24][CH:23]=[N:22]2)=[CH:19][CH:20]=1)#[N:14]

Participants

5

Reactant 3

HCID 6329Methylamine2×HCID 682631,1'-CarbonyldiimidazoleHCID 121393726HCID 121393726, compound

Product 1

HCID 121393767HCID 121393767, compoundYield 52.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

1,1′-carbonyl diimidazole (45 mg, 0.278 mmol) was added to a solution of {5-[1-(4-cyanophenyl)-1H-pyrazol-5-yl]-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1H-imidazol-1-yl}acetic acid (Example 22) (65 mg, 0.139 mmol) in THF (2.0 mL). The mixture was stirred for 1.25 h then a 2M methylamine in THF (0.278 mL, 0.556 mmol) was added. The mixture was stirred for 45 min then a second aliquot of 2M methylamine in THF (0.278 mL, 0.556 mmol) was added. The mixture was stirred for a further 40 minutes then partitioned between EtOAc and water. The phases were partitioned. The organic phase was dried over Na2SO4 and evaporated. The product was purified by chromatography on a 12 g silica gel column, eluting with 5% methanol in DCM. The material thus obtained was freeze dried from acetonitrile-water to afford the title compound (35 mg) a white solid.

Workup

  1. stirringThe mixture was stirred for 45 min
  2. stirringThe mixture was stirred for a further 40 minutes
  3. customthen partitioned between EtOAc and water
  4. customThe phases were partitioned
  5. dry with materialThe organic phase was dried over Na2SO4
  6. customevaporated
  7. customThe product was purified by chromatography on a 12 g silica gel column
  8. washeluting with 5% methanol in DCM
  9. customThe material thus obtained
  10. dry with materialdried from acetonitrile-water

Sources & evidence

ORD record
ord-68d72adb094e4af8ad6207d10f87efd9
Source dataset
uspto-grants-2016_08
Patent number
US09409870B2

Reaction notes

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