Dichloromethane → 6-tert-Butyl-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-phthalazin-1-one

HRID 68465Notes

Reaction equation

HRID 68465 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:16]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]3[CH:29]=[C:28]([NH:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]([N:39]5[CH2:44][CH2:43][O:42][CH2:41][CH2:40]5)=[O:38])=[CH:33][N:32]=4)[C:27](=[O:45])[N:26]([CH3:46])[CH:25]=3)[C:17]=1[CH:18]=[O:19])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.[BH4-].[Na+]>CO>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:16]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]3[CH:29]=[C:28]([NH:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]([N:39]5[CH2:40][CH2:41][O:42][CH2:43][CH2:44]5)=[O:38])=[CH:33][N:32]=4)[C:27](=[O:45])[N:26]([CH3:46])[CH:25]=3)[C:17]=1[CH2:18][OH:19])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6344Dichloromethane2×HCID 4311764Sodium borohydrideHCID 580161872-(6-tert-Butyl-1-oxo-1H-phthalazin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzaldehyde

Product 1

HCID 445537256-tert-Butyl-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-phthalazin-1-oneYield 76.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

121 mg (0.20 mmol) of 2-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzaldehyde was weighed into a 20 mL reaction vial fitted with a stir bar and septum. Added 4 mL of CH2Cl2 and 2 mL MeOH and stirred to obtain a clear amber solution. Added 1.1 mL (0.29 mmol) of a freshly prepared 10 mg/mL solution of sodium borohydride in MeOH. Stirred at room temperature for 3 hr. Quenched the reaction with 5 mL of saturated aqueous NH4Cl. Added 5 mL of CH2Cl2 to the reaction mixture and separated phases. Washed the organic phase with 5 mL brine, dried over Na2SO4, and removed the solvent on rotavap. Added 2 mL acetonitrile to the residue and immersed the vial in an ultrasonic bath. The residue dissolved momentarily, then a white precipitate rapidly crystallized out of solution. Added 5 mL Et2O to the mixture and collected the precipitate by filtration. Dried under high vacuum to obtain 95 mg of the title compound as an off-white solid. MS (ESI) 621 (M+H)+.

Workup

  1. customvial fitted with a stir bar
  2. customto obtain a clear amber solution
  3. stirringStirred at room temperature for 3 hr
  4. customQuenched
  5. customthe reaction with 5 mL of saturated aqueous NH4Cl
  6. customseparated phases
  7. washWashed the organic phase with 5 mL brine
  8. dry with materialdried over Na2SO4
  9. customremoved the solvent on rotavap
  10. additionAdded 2 mL acetonitrile to the residue
  11. dissolutionThe residue dissolved momentarily
  12. customa white precipitate rapidly crystallized out of solution
  13. additionAdded 5 mL Et2O to the mixture
  14. customcollected the precipitate
  15. filtrationby filtration
  16. customDried under high vacuum

Sources & evidence

ORD record
ord-911cb757bfae4a6985984d0a1424fff7
Source dataset
uspto-grants-2014_09
Patent number
US08822457B2

Reaction notes

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