Diisopropylethylamine → 4-amino-2-fluoro-5-methoxy-N-[[1-(pyrrolidin-1-ylmethyl)cyclopropyl]methyl]benzamide

HRID 2234508Notes

Reaction equation

HRID 2234508 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.[N:14]1([CH2:19][C:20]2([CH2:23][NH2:24])[CH2:22][CH2:21]2)[CH2:18][CH2:17][CH2:16][CH2:15]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:5]([C:6]([NH:24][CH2:23][C:20]2([CH2:19][N:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[CH2:21][CH2:22]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 280647661-{1-[(Pyrrolidin-1-yl)methyl]cyclopropyl}methanamine2×HCID 529829634-Amino-2-fluoro-5-methoxybenzoic acid2×

Product 1

HCID 686847514-amino-2-fluoro-5-methoxy-N-[[1-(pyrrolidin-1-ylmethyl)cyclopropyl]methyl]benzamideYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-amino-2-fluoro-5-methoxy-benzoic acid (Intermediate 183; 500 mg, 2.70 mmol), [1-(pyrrolidin-1-ylmethyl)cyclopropyl]methanamine (Intermediate 33; 417 mg, 2.70 mmol), HATU (1.545 g, 4.05 mmol) and DIPEA (1.415 mL, 8.10 mmol) were dissolved in DMF (8 mL) and left to stir for 3 hours at room temperature. The reaction mixture was loaded onto an SCX-3 column pre-washed with methanol. The column was washed with methanol eluted with 2% 7N ammonia/methanol. Product containing fractions were combined and evaporated and the residue purified on a silica column (5-12% MeOH ammonia/DCM gradient elution) to yield the title compound as an orange-brown solid (200 mg, 23%).

Workup

  1. waitleft
  2. washpre-washed with methanol
  3. washThe column was washed with methanol
  4. washeluted with 2% 7N ammonia/methanol
  5. additionProduct containing fractions
  6. customevaporated
  7. customthe residue purified on a silica column (5-12% MeOH ammonia/DCM gradient elution)

Sources & evidence

ORD record
ord-021a959f7b4d45ae99335f2bccb57ed5
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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