Diisopropylamine → N-(3,4-Dichlorophenyl)-4-{[(2R)-4-isopropylpiperazin-2-yl]carbonyl}piperazine-1-carboxamide

HRID 603250Notes

Reaction equation

HRID 603250 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([NH:10][C:11]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[O:12])[CH:6]=[CH:7][C:8]=1[Cl:9].C(OC([N:26]1[CH2:31][CH2:30][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:28][C@@H:27]1[C:35](O)=[O:36])=O)(C)(C)C.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(NC(C)C)(C)C>C1COCC1>[Cl:2][C:3]1[CH:4]=[C:5]([NH:10][C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:35]([C@H:27]3[CH2:28][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:30][CH2:31][NH:26]3)=[O:36])[CH2:15][CH2:14]2)=[O:12])[CH:6]=[CH:7][C:8]=1[Cl:9]

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 46743200N-(3,4-dichlorophenyl)piperazine-1-carboxamide hydrochlorideHCID 51440433(2R)-1-(tert-butoxycarbonyl)-4-isopropylpiperazine-2-carboxylic acid

Product 1

HCID 57656833N-(3,4-Dichlorophenyl)-4-{[(2R)-4-isopropylpiperazin-2-yl]carbonyl}piperazine-1-carboxamideYield 30.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-(3,4-Dichlorophenyl)piperazine-1-carboxamide hydrochloride (251 mg) and (2R)-1-(tert-Butoxycarbonyl)-4-isopropylpiperazine-2-carboxylic acid (200 mg) were dissolved in dry THF (10 mL) followed by addition of N,N-di-isopropylethylamine (0.26 ml) and HATU (335 mg) and the reaction was stirred for 4 h. A further 0.26 ml of N,N-di-iso-propylamine was added and the reaction was stirred for 18 h at rt. The solvent was evaporated under reduced pressure then redissolved in dichloromethane (50 ml) followed by washing with sat. aqueous NaHCO3 (20 ml). The organic layer was separated on a phase separation cartridge and evaporated. Purification by chromatography (3-10% methanol:dichloromethane) afforded the crude product (180 mg) as a foam which was used without further purification. The foam was then dissolved in TFA/DCM (1:1, 10 ml) and stirred for 30 mins. The solvent was removed under reduced pressure then taken up in 1M. aqueous sodium hydroxide (30 ml) and extracted with dichloromethane (2×30 ml). The organic layer was separated on a phase separation cartridge and evaporated. Purification by chromatography (5-25% MeOH:DCM) afforded the title compound (95 mg) as a white foam

Workup

  1. stirringthe reaction was stirred for 18 h at rt
  2. customThe solvent was evaporated under reduced pressure
  3. dissolutionthen redissolved in dichloromethane (50 ml)
  4. washby washing with sat. aqueous NaHCO3 (20 ml)
  5. customThe organic layer was separated on a phase separation cartridge
  6. customevaporated
  7. customPurification by chromatography (3-10% methanol:dichloromethane)
  8. customafforded the crude product (180 mg) as a foam which
  9. customwas used without further purification
  10. dissolutionThe foam was then dissolved in TFA/DCM (1:1, 10 ml)
  11. stirringstirred for 30 mins
  12. customThe solvent was removed under reduced pressure
  13. extractionaqueous sodium hydroxide (30 ml) and extracted with dichloromethane (2×30 ml)
  14. customThe organic layer was separated on a phase separation cartridge
  15. customevaporated
  16. customPurification by chromatography (5-25% MeOH:DCM)

Sources & evidence

ORD record
ord-3364ad1570d8424ea83e20f16e6911e5
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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