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 1916071Notes

Reaction equation

HRID 1916071 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-d8f7627c210f40e7aad1e77485a6808b
Source dataset
uspto-grants-2013_12
Patent number
US08618098B2

Reaction notes

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