Diisopropylethylamine → 5-chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-N-(1-methyl-4-piperidyl)benzamide

HRID 2234310Notes

Reaction equation

HRID 2234310 reaction equation
[Cl:1][C:2]1[C:3]([NH:12][C:13]2[N:23]=[C:22]3[C:16]([N:17]([CH3:30])[C:18](=[O:29])[CH2:19][CH2:20][N:21]3[CH:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)=[CH:15][N:14]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7](O)=[O:8].[NH2:31][CH:32]1[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Cl:1][C:2]1[C:3]([NH:12][C:13]2[N:23]=[C:22]3[C:16]([N:17]([CH3:30])[C:18](=[O:29])[CH2:19][CH2:20][N:21]3[CH:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)=[CH:15][N:14]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:31][CH:32]1[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]1)=[O:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 686827155-Chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-benzoic acid2×

Product 1

HCID 686849065-chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-N-(1-methyl-4-piperidyl)benzamideYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

5-chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-benzoic acid (Intermediate 219; 100 mg, 0.23 mmol), 4-amino-1-methylpiperidine (Fluorochem; 40 mg, 0.35 mmol) and HATU (132 mg, 0.35 mmol) were stirred in DMF (3 mL). N,N-diisopropylethylamine (121 μl, 0.69 mmol) was added and the mixture heated at 50° C. for 2 hours. The mixture was cooled and absorbed on to an SCX column, which was subsequently washed with methanol and eluted with ammonia in methanol. Product containing fractions were concentrated and the residue purified by base modified reverse phase preparative chromatography to yield the title compound as a white solid (58 mg, 48%)

Workup

  1. temperatureThe mixture was cooled
  2. customabsorbed on to an SCX column, which
  3. washwas subsequently washed with methanol
  4. washeluted with ammonia in methanol
  5. additionProduct containing fractions
  6. concentrationwere concentrated
  7. customthe residue purified by base modified reverse phase preparative chromatography

Sources & evidence

ORD record
ord-93f2d3aa61fc497a8870a121a0d1c2e2
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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