Potassium Carbonate → AZD1305

HRID 1992367Notes

Reaction equation

HRID 1992367 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][CH2:13][N:14]1[CH2:21][CH:20]2[O:22][CH:16]([CH2:17][NH:18][CH2:19]2)[CH2:15]1)[C:6]#[N:7].Br[CH2:24][CH2:25][NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:29]([O:28][C:27](=[O:33])[NH:26][CH2:25][CH2:24][N:18]1[CH2:19][CH:20]2[O:22][CH:16]([CH2:15][N:14]([CH2:13][CH2:12][O:11][C:10]3[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=3[F:2])[CH2:21]2)[CH2:17]1)([CH3:32])([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 67096470HCID 67096470, compound

Product 1

HCID 15605092AZD1305Yield 77.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of intermediate 3-fluoro-4-[2-(9-oxa-3,7-diaza-bicyclo[3.3.1]non-3-yl)-ethoxy]-benzonitrile hydrochloride (5 g, 0.0137 mol, from step (vii) above), and tert-butyl 2-bromoethylcarbamate (3.98 g, 0.0178 mol , see WO 01/28992) and potassium carbonate (7.57 g, 0.0548 mol) in dry acetonitrile (100 ml) was stirred at 60° C. overnight under nitrogen atmosphere. The reaction mixture was filtered through celite and filtrate was concentrated under reduced pressure. The residue was purified by column chromatography over silica gel using 5% methanol in dichloromethane as eluent to give the sub-title compound (4.6 g) as an oil.

Workup

  1. filtrationThe reaction mixture was filtered through celite and filtrate
  2. concentrationwas concentrated under reduced pressure
  3. customThe residue was purified by column chromatography over silica gel using 5% methanol in dichloromethane as eluent

Sources & evidence

ORD record
ord-e10cd0a3b1414ea2b6eb5b95d63a1f1a
Source dataset
uspto-grants-2010_01
Patent number
US07648985B2

Reaction notes

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