Diisopropylethylamine → 4-amino-2-fluoro-5-methoxy-N-[(3R)-1-methylpyrrolidin-3-yl]benzamide

HRID 2234452Notes

Reaction equation

HRID 2234452 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.CN(C(ON1N=[N:29][C:24]2[CH:25]=[CH:26][CH:27]=[N:28][C:23]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.CN1CC[C@@H](N)C1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[NH2:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:5]([C:6]([NH:29][C@@H:24]2[CH2:25][CH2:26][N:28]([CH3:27])[CH2:23]2)=[O:8])=[C:4]([F:13])[CH:3]=1

Participants

6

Reactant 4

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×HCID 53256048(3R)-1-Methyl-3-PyrrolidinaMine hydrochloride2×

Product 1

HCID 686817384-amino-2-fluoro-5-methoxy-N-[(3R)-1-methylpyrrolidin-3-yl]benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-amino-2-fluoro-5-methoxybenzoic acid (Intermediate 183; 500 mg, 2.70 mmol), HATU (1.55 g, 4.05 mmol) and (3R)-1-methylpyrrolidin-3-amine di Hydrochloride (Intermediate 184; 631 mg, 3.31 mmol) were stirred in DMF (7.5 mL) and diisopropylethylamine (2.36 ml, 13.50 mmol) added. The reaction mixture was stirred for 2 hours and then absorbed on to an SCX column, which was then washed with methanol and eluted with ammonia in methanol. Product containing fractions were concentrated and purified by column chromatography (2.5% ammonia in methanol/DCM) to yield the title compound as a viscous brown oil. (662 mg, 92%).

Workup

  1. customabsorbed on to an SCX column, which
  2. washwas then washed with methanol
  3. washeluted with ammonia in methanol
  4. additionProduct containing fractions
  5. concentrationwere concentrated
  6. custompurified by column chromatography (2.5% ammonia in methanol/DCM)

Sources & evidence

ORD record
ord-9151270f56584d08893fd806553bd949
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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