Potassium Carbonate → 3-[4'-(5-fluoro-2,3-dihydro-indole-1-carbonyl)-6'-methoxy-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl]-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

HRID 2059979Notes

Reaction equation

HRID 2059979 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11](=[O:13])[N:10]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[CH2:9][CH2:8][C:7]=2[CH:20]=1.Cl[C:22]1[CH:27]=[C:26]([C:28]([N:30]2[C:38]3[C:33](=[CH:34][C:35]([F:39])=[CH:36][CH:37]=3)[CH2:32][CH2:31]2)=[O:29])[CH:25]=[C:24]([O:40][CH3:41])[N:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1.CN(C=O)C>[F:39][C:35]1[CH:34]=[C:33]2[C:38](=[CH:37][CH:36]=1)[N:30]([C:28]([C:26]1[CH:25]=[C:24]([O:40][CH3:41])[N:23]=[C:22]([N:17]3[CH2:18][CH2:19][CH:14]([N:10]4[CH2:9][CH2:8][C:7]5[CH:20]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=5[NH:12][C:11]4=[O:13])[CH2:15][CH2:16]3)[CH:27]=1)=[O:29])[CH2:31][CH2:32]2

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 183568527-methoxy-3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 58386441(2-Chloro-6-methoxypyridin-4-yl)-(5-fluoro-2,3-dihydroindol-1-yl)-methanone

Product 1

HCID 426138053-[4'-(5-fluoro-2,3-dihydro-indole-1-carbonyl)-6'-methoxy-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl]-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 0.633 g (2.30 mmol) 7-methoxy-3-piperidin-4-yl-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one, 0.700 mg (2.28 mmol) (2-chloro-6-methoxypyridin-4-yl)-(5-fluoro-2,3-dihydroindol-1-yl)-methanone and 954 mg (6.90 mmol) potassium carbonate in 5.0 mL NMP was stirred for 8 h at 130° C. After cooling the reaction mixture to RT the precipitate formed was filtered off and purified by preparative HPLC. The fractions containing the product were combined and evaporated down i. vac. The residue obtained was digested in DMF and the product remaining as a solid was suction filtered and dried i. vac. The mother liquor was again purified by preparative HPLC, the fractions containing product were combined and evaporated down i. vac. The residue was triturated with ethanol, the solid product was suction filtered and dried i. vac.

Workup

  1. temperatureAfter cooling the reaction mixture to RT the precipitate
  2. customformed
  3. filtrationwas filtered off
  4. custompurified by preparative HPLC
  5. additionThe fractions containing the product
  6. customevaporated down i
  7. customThe residue obtained
  8. filtrationfiltered
  9. customdried i
  10. customThe mother liquor was again purified by preparative HPLC
  11. additionthe fractions containing product
  12. customevaporated down i
  13. customThe residue was triturated with ethanol
  14. filtrationfiltered
  15. customdried i

Sources & evidence

ORD record
ord-d9415d70be3f4a92b3161dd483dcaa4b
Source dataset
uspto-grants-2012_10
Patent number
US08278336B2

Reaction notes

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