Sodium Carbonate → (2-Chloro-4-naphthalen-1-yl-phenyl)-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4] benzodiazepin-10-yl)-methanone

HRID 1830068Notes

Reaction equation

HRID 1830068 reaction equation
[C:1]1(B(O)O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Br[C:15]1[CH:20]=[CH:19][C:18]([C:21]([N:23]2[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[CH2:27][N:26]3[CH:34]=[CH:35][CH:36]=[C:25]3[CH2:24]2)=[O:22])=[C:17]([Cl:37])[CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:37][C:17]1[CH:16]=[C:15]([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)[CH:20]=[CH:19][C:18]=1[C:21]([N:23]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH2:27][N:26]2[CH:34]=[CH:35][CH:36]=[C:25]2[CH2:24]1)=[O:22]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2545321-Naphthaleneboronic acidHCID 9909050HCID 9909050, compound

Product 1

HCID 21947737(2-Chloro-4-naphthalen-1-yl-phenyl)-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4] benzodiazepin-10-yl)-methanone

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

1-Naphthaleneboronic acid (0.52 g, 3.00 mmol) was added to a mixture of (4-bromo-2-chlorophenyl)-(5H, 11H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone of Step A (1.27 g, 3.15 mmol) and sodium carbonate (0.53 g, 4.98 mmol) in toluene (22.5 mL), ethanol (4.5 mL) and water (9 mL). The resultant solution was purged with nitrogen for 10 minutes, then tetrakis(triphenylphosphine)palladium (0.18 g, 0.06 mmol) was added. The reaction mixture was heated to reflux for 76 hours. The solution was cooled to ambient temperature, then filtered through a pad of Celite, which was subsequently rinsed with ethyl acetate. The combined filtrate was diluted to 100 mL water/ethyl acetate (1:1). The aqueous layer was extracted with ethyl acetate, and the combined organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness to yield a brown oil. Purification by flash chromatography on silica gel eluting with hexane-ethyl acetate (5:1) resulted in a white solid which was dried under vacuum (0.62 g), m.p. 115–117.5° C.

Workup

  1. customThe resultant solution was purged with nitrogen for 10 minutes
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 76 hours
  4. filtrationfiltered through a pad of Celite, which
  5. washwas subsequently rinsed with ethyl acetate
  6. additionThe combined filtrate was diluted to 100 mL water/ethyl acetate (1:1)
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. dry with materialthe combined organic layer was dried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customto yield a brown oil
  12. customPurification by flash chromatography on silica gel eluting with hexane-ethyl acetate (5:1)
  13. customresulted in a white solid which
  14. customwas dried under vacuum (0.62 g), m.p. 115–117.5° C.

Sources & evidence

ORD record
ord-7f7fd2463bc24e29a04ba1697dd80458
Source dataset
uspto-grants-2006_06
Patent number
US07064120B2

Reaction notes

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