Diisopropylethylamine → 4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-N-(1-propyl-4-piperidyl)benzamide

HRID 2234308Notes

Reaction equation

HRID 2234308 reaction equation
[CH:1]1([N:6]2[CH2:16][CH2:15][C:14](=[O:17])[N:13]([CH3:18])[C:12]3[C:7]2=[N:8][C:9]([NH:19][C:20]2[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][C:21]=2[O:29][CH3:30])=[N:10][CH:11]=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:64][CH:65]1[CH2:70][CH2:69][N:68]([CH2:71][CH2:72][CH3:73])[CH2:67][CH2:66]1>CC(N(C)C)=O.CO>[CH:1]1([N:6]2[CH2:16][CH2:15][C:14](=[O:17])[N:13]([CH3:18])[C:12]3[C:7]2=[N:8][C:9]([NH:19][C:20]2[CH:28]=[CH:27][C:23]([C:24]([NH:64][CH:65]4[CH2:70][CH2:69][N:68]([CH2:71][CH2:72][CH3:73])[CH2:67][CH2:66]4)=[O:25])=[CH:22][C:21]=2[O:29][CH3:30])=[N:10][CH:11]=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5417301-Propylpiperidin-4-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 426102404-(9-cyclopentyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid

Product 1

HCID 686836184-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-N-(1-propyl-4-piperidyl)benzamideYield 65%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 31374DimethylacetamideSolvent

Procedure

4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-benzoic acid (Example 111; 231 mg, 0.56 mmol), DIPEA (0.3 mL, 1.68 mmol) and HATU (283 mg, 0.75 mmol) were stirred together in DMA (4 mL) at ambient temperature for 10 minutes. 4-amino-1-propylpiperidine (Fluorochem; 100 mg, 0.70 mmol) was added and the mixture stirred at room temperature for 4 hours. The reaction mixture was loaded onto an SCX-2 (10 g) column pre-wet with MeOH. The column was washed with MeOH (×2) and the product eluted with 2M NH3/MeOH. Product containing fractions were combined and evaporated and the residue purified by base modified reverse phase preparative HPLC. Product containing fractions were combined and evaporated to yield the title compound as a gum (194 mg, 65%).

Workup

  1. washThe column was washed with MeOH (×2)
  2. washthe product eluted with 2M NH3/MeOH
  3. additionProduct containing fractions
  4. customevaporated
  5. customthe residue purified by base modified reverse phase preparative HPLC
  6. additionProduct containing fractions
  7. customevaporated

Sources & evidence

ORD record
ord-512e18277659408da33fa8b903bce388
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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