Dimethylformamide → HCID 68684046, compound

HRID 2234472Notes

Reaction equation

HRID 2234472 reaction equation
[NH2:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([F:13])[CH:3]=1.[CH3:14][N:15](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C[CH2:39][N:40]([CH:44]([CH3:46])[CH3:45])[CH:41]([CH3:43])[CH3:42].[CH3:47]N(C=O)C>>[NH2:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:5]([C:6]([NH:15][CH:14]2[CH2:43][C@H:41]3[N:40]([CH3:39])[C@H:44]([CH2:46][CH2:47][CH2:42]3)[CH2:45]2)=[O:8])=[C:4]([F:13])[CH:3]=1

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 529829634-Amino-2-fluoro-5-methoxybenzoic acid2×

Product 1

HCID 68684046HCID 68684046, compoundYield 69%

Procedure

4-amino-2-fluoro-5-methoxybenzoic acid (Intermediate 183; 0.75 g, 4.07 mmol), HATU (1.70 g, 4.48 mmol) and DIPEA (2.1 mL, 12.21 mmol) were stirred together in DMF (10 mL) for 10 minutes. Endo-9-methyl-9-azabicyclo[3,3,1]-nonan-3-amine (Chempacific; 0.69 g, 4.48 mmol) in DMF (1 mL) was added and the brown solution stirred at ambient temperature for 2 hours. The solvent was evaporated and the residue dissolved in MeOH and loaded onto an SCX-2 (20 g) column pre-wet with MeOH. The column was washed with MeOH (2 column volumes) and the product eluted with 2M NH3/MeOH (2 column volumes). Product containing fractions were combined and evaporated and the resultant material purified on a silica column eluting with 0-10% 2M NH3/MeOH/DCM). Product containing fractions were combined and evaporated to yield the title compound as a dark brown gum (897 mg, 69%).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue dissolved in MeOH
  3. washThe column was washed with MeOH (2 column volumes)
  4. washthe product eluted with 2M NH3/MeOH (2 column volumes)
  5. additionProduct containing fractions
  6. customevaporated
  7. customthe resultant material purified on a silica column
  8. washeluting with 0-10% 2M NH3/MeOH/DCM)
  9. additionProduct containing fractions
  10. customevaporated

Sources & evidence

ORD record
ord-ed874c9b1075486fbec00f35ef40a240
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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