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

HRID 2234474Notes

Reaction equation

HRID 2234474 reaction equation
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([F:12])[CH:3]=1.CN(C(ON1N=[N:28][C:23]2[CH:24]=[CH:25][CH:26]=[N:27][C:22]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]([Cl:11])=[CH:9][C:5]([C:6]([NH:28][C@@H:23]2[CH2:24][CH2:25][N:27]([CH3:26])[CH2:22]2)=[O:8])=[C:4]([F:12])[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 53256048(3R)-1-Methyl-3-PyrrolidinaMine hydrochloride2×HCID 686839334-Amino-5-chloro-2-fluorobenzoic acid2×

Product 1

HCID 686875884-amino-5-chloro-2-fluoro-N-[(3R)-1-methylpyrrolidin-3-yl]benzamideYield 77.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-amino-5-chloro-2-fluorobenzoic acid (Intermediate 176; 300 mg, 1.58 mmol), HATU (903 mg, 2.37 mmol) and (3R)-1-methylpyrrolidin-3-amine di Hydrochloride (Intermediate 184; 325 mg, 2.37 mmol) were stirred in DMF (5 mL) and diisopropylethylamine (1.2 mL, 7.12 mmol) added. The mixture was stirred for 2 hours at room temperature and then absorbed on to an SCX column, washed with methanol and eluted with ammonia in methanol. Product containing fractions were concentrated and purified by column chromatography (5% ammonia in methanol/DCM) to yield the title compound as a pale orange solid (333 mg, 77%).

Workup

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

Sources & evidence

ORD record
ord-2c7c543f60624e65a1fe74fe3bd894b3
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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