Sodium cyanoborohydride → 7-tert-Butyl-3-(2-methyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-2,3-dihydro-1H-quinazolin-4-one

HRID 600359Notes

Reaction equation

HRID 600359 reaction equation
[C:1]([C:5]1[CH:14]=[C:13]2[C:8]([C:9](=[O:45])[N:10]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]4[CH:26]=[C:25]([NH:27][C:28]5[CH:33]=[CH:32][C:31]([C:34]([N:36]6[CH2:41][CH2:40][O:39][CH2:38][CH2:37]6)=[O:35])=[CH:30][N:29]=5)[C:24](=[O:42])[N:23]([CH3:43])[N:22]=4)[C:16]=3[CH3:44])[CH:11]=[N:12]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([BH3-])#N.[Na+]>CO.Cl>[C:1]([C:5]1[CH:14]=[C:13]2[C:8]([C:9](=[O:45])[N:10]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]4[CH:26]=[C:25]([NH:27][C:28]5[CH:33]=[CH:32][C:31]([C:34]([N:36]6[CH2:41][CH2:40][O:39][CH2:38][CH2:37]6)=[O:35])=[CH:30][N:29]=5)[C:24](=[O:42])[N:23]([CH3:43])[N:22]=4)[C:16]=3[CH3:44])[CH2:11][NH:12]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 252655857-tert-Butyl-3-(2-methyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-3H-quinazolin-4-one

Product 1

HCID 445535587-tert-Butyl-3-(2-methyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-2,3-dihydro-1H-quinazolin-4-oneYield 61.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 887MethanolSolvent2×

Procedure

To a mixture of 7-tert-Butyl-3-(2-methyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-3H-quinazolin-4-one (11 mg, 0.018 mmol) and sodium cyanoborohydride (1.3 mg, 0.019 mmol) in 1 mL methanol was added 1 drop of 2M hydrochloric acid in methanol to bring the pH to 3. After stirring for 45 minutes, the resulting mixture was partitioned between ethylacetate and dilute aqueous NaHCO3. The ethylacetate layer was washed with brine, dried over anhydrous MgSO4, concentrated in vacuo, and purified by preparative TLC (5% MeOH/CH2Cl2) to yield 7-tert-Butyl-3-(2-methyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-2,3-dihydro-1H-quinazolin-4-one (6.5 mg, 0.011 mmol). MS (ESI) 608 (M+H)+.

Workup

  1. customthe resulting mixture was partitioned between ethylacetate and dilute aqueous NaHCO3
  2. washThe ethylacetate layer was washed with brine
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationconcentrated in vacuo
  5. custompurified by preparative TLC (5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-744ce6a950884391b315c6ca6dc98c1c
Source dataset
uspto-grants-2011_03
Patent number
US07902194B2

Reaction notes

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