Diisopropylethylamine → 3-{1-[6-Chloro-5-(3,4-dimethyl-2-oxo-2,3-dihydro-benzoxazole-6-carbonyl)-pyridazin-3-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

HRID 469336Notes

Reaction equation

HRID 469336 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]2[NH:7][C:8](=[O:18])[N:9]([CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:10][CH2:11][C:5]=2[CH:4]=1.[Cl:21][C:22]1[N:23]=[N:24][C:25](Cl)=[CH:26][C:27]=1[C:28]([C:30]1[CH:40]=[C:39]([CH3:41])[C:33]2[N:34]([CH3:38])[C:35](=[O:37])[O:36][C:32]=2[CH:31]=1)=[O:29].CCN(C(C)C)C(C)C>CN(C=O)C.[Cu]Br>[Cl:21][C:22]1[N:23]=[N:24][C:25]([N:15]2[CH2:14][CH2:13][CH:12]([N:9]3[CH2:10][CH2:11][C:5]4[CH:4]=[C:3]([O:2][CH3:1])[CH:20]=[CH:19][C:6]=4[NH:7][C:8]3=[O:18])[CH2:17][CH2:16]2)=[CH:26][C:27]=1[C:28]([C:30]1[CH:40]=[C:39]([CH3:41])[C:33]2[N:34]([CH3:38])[C:35](=[O:37])[O:36][C:32]=2[CH:31]=1)=[O:29]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 183568527-methoxy-3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 581811216-(3,6-dichloro-pyridazine-4-carbonyl)-3,4-dimethyl-3H-benzoxazol-2-one

Product 1

HCID 252708103-{1-[6-Chloro-5-(3,4-dimethyl-2-oxo-2,3-dihydro-benzoxazole-6-carbonyl)-pyridazin-3-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 6228DimethylformamideSolvent

Procedure

550 mg (2.00 mmol) 7-methoxy-3-piperidin-4-yl-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one, 610 mg (1.80 mmol) 6-(3.6-dichloro-pyridazine-4-carbonyl)-3,4-dimethyl-3H-benzoxazol-2-one, 630 mg (4.39 mmol) copper(I)bromide and 430 mL (2.50 mmol) DIPEA in 5 mL DMF were stirred for 2 h at 110° C., then cooled and filtered. The filtrate was combined with 1 mL of a 1N aqueous hydrochloric acid solution and precipitated with 40 mL ice water. The precipitate was suction filtered, washed with water and dried. The solid was stirred with 120 mL DCM/MeOH (11:1), filtered through silica gel and washed with DCM/MeOH. The filtrate was evaporated down. The residue was triturated with diethyl ether, suction filtered and dried. A mixture of isomers was obtained which was further reacted.

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. customprecipitated with 40 mL ice water
  4. filtrationfiltered
  5. washwashed with water
  6. customdried
  7. filtrationfiltered through silica gel
  8. washwashed with DCM/MeOH
  9. customThe filtrate was evaporated down
  10. customThe residue was triturated with diethyl ether, suction
  11. filtrationfiltered
  12. customdried
  13. additionA mixture of isomers
  14. customwas obtained which

Sources & evidence

ORD record
ord-61dda9b253e948e1a8f3df6c437a6aef
Source dataset
uspto-grants-2014_01
Patent number
US08629137B2

Reaction notes

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