Cesium carbonate → 6-Chloro-2-methyl-4-({5-[(morpholin-4-yl)carbonyl]pyridin-2-yl}amino)-2,3-dihydropyridazin-3-one

HRID 337282Notes

Reaction equation

HRID 337282 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.Br[C:17]1[C:18](=[O:25])[N:19]([CH3:24])[N:20]=[C:21]([Cl:23])[CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:23][C:21]1[CH:22]=[C:17]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)=[O:9])=[CH:6][N:7]=2)[C:18](=[O:25])[N:19]([CH3:24])[N:20]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-oneHCID 59259223(6-Aminopyridin-3-yl)(morpholino)methanone

Product 1

HCID 576627786-Chloro-2-methyl-4-({5-[(morpholin-4-yl)carbonyl]pyridin-2-yl}amino)-2,3-dihydropyridazin-3-oneYield 71.7%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
93 °C

Procedure

(6-Aminopyridin-3-yl)(morpholino)methanone (58 g, 280 mmol, Eq: 1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (63.66 g, 285 mmol, Eq: 1.02) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.86 g, 8.4 mmol, Eq: 0.03) were dissolved in DMF (1.1 l) under heating. Cesium carbonate (274 g, 840 mmol, Eq: 3) was added. Finally Pd2 (dba)3 (3.84 g, 4.2 mmol, Eq: 0.015) was added under an argon atmosphere. The reaction mixture was heated to 93° C. (internal temperature) for 3 hr. The warm reaction mixture was poured into water/ice (10 l). A beige precipitate was collected by filtration and washed with water (2 l). The resulting solid was taken up in DCM (51) and filtered. The filtrate was concentrated in vacuo to give a solid, which was triturated with isopropanol (700 ml), filtered and dried under vacuum to afford the desired product (70.24 g) as a beige solid. (M+H)+=350 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.56-3.79 (m, 8 H) 3.83 (s, 3 H) 6.96 (d, J=8.31 Hz, 1 H) 7.77 (dd, J=8.31, 2.27 Hz, 1 H) 8.34-8.42 (m, 2 H) 8.47 (d, J=2.27 Hz, 1 H).

Workup

  1. temperatureunder heating
  2. customThe warm reaction mixture
  3. filtrationA beige precipitate was collected by filtration
  4. washwashed with water (2 l)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customto give a solid, which
  8. customwas triturated with isopropanol (700 ml)
  9. filtrationfiltered
  10. customdried under vacuum

Sources & evidence

ORD record
ord-5ed7d8f94fdc40f080dc2f9a0774a778
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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