2-Bromomethylnaphthalene → HCID 67283244, compound

HRID 1910678Notes

Reaction equation

HRID 1910678 reaction equation
[Cl:1][C:2]1[CH:27]=[CH:26][C:5]2[N:6]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[C:7](=[O:16])[CH2:8][N:9]=[C:10]([C:11]3[CH:12]=[N:13][NH:14][CH:15]=3)[C:4]=2[CH:3]=1.CC([O-])(C)C.[K+].Br[CH2:35][C:36]1[CH:45]=[CH:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:37]=1>C1COCC1>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]2[N:6]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[C:7](=[O:16])[CH:8]([CH2:35][C:36]3[CH:45]=[CH:44][C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[CH:37]=3)[N:9]=[C:10]([C:11]3[CH:15]=[N:14][NH:13][CH:12]=3)[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 703202-BromomethylnaphthaleneHCID 23665647Potassium tert-butoxideHCID 67282355HCID 67282355, compound

Product 1

HCID 67283244HCID 67283244, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

7-Chloro-1-(4-methoxybenzyl)-5-(1H-pyrazol-4-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (163 mg) was dissolved in THF (3 mL) and the solution was cooled to −78° C. A solution of KOtBu in THF (1 M, 1.1 mL, 2.6 eq) was then added dropwise and the anion was stirred for 10 minutes. 2-Bromomethyl naphthalene (123 mg, 1.3 eq) was then added and the reaction was allowed to warm to room temperature where it was held for 2 hours. The reaction was then quenched with saturated aqueous ammonium chloride and the crude product was partitioned between water and EtOAc. The organic fraction was washed with brine, then dried over sodium sulfate, and concentrated onto silica gel then purified by flash chromatography (gradient: 3:1 hexanes:EtOAc to EtOAc) delivering the product as a solid (106 mg, 48% yield). MS (ES+) m/z 521.2 (M+1).

Workup

  1. temperatureto warm to room temperature where it
  2. waitwas held for 2 hours
  3. customThe reaction was then quenched with saturated aqueous ammonium chloride
  4. customthe crude product was partitioned between water and EtOAc
  5. washThe organic fraction was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated onto silica gel
  8. customthen purified by flash chromatography (gradient: 3:1 hexanes:EtOAc to EtOAc)

Sources & evidence

ORD record
ord-871bd224ad3c45a5a9e2279517b9c9c4
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

Loading…