Triethylamine → Azd 7009

HRID 500506Notes

Reaction equation

HRID 500506 reaction equation
C([N:3](CC)CC)C.Br[CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15].[OH:19][C@@H:20]([CH2:31][N:32]1[CH2:39][CH:38]2[O:40][CH:34]([CH2:35][NH:36][CH2:37]2)[CH2:33]1)[CH2:21][O:22][C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=1>CN(C=O)C>[OH-:13].[NH4+:3].[C:27]([C:26]1[CH:25]=[CH:24][C:23]([O:22][CH2:21][C@@H:20]([OH:19])[CH2:31][N:32]2[CH2:33][CH:34]3[O:40][CH:38]([CH2:37][N:36]([CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:35]3)[CH2:39]2)=[CH:30][CH:29]=1)#[N:28]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 684578084-{[(2S)-2-Hydroxy-3-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]-oxy}benzonitrile

Product 2

HCID 14923Ammonium HydroxideHCID 9876235Azd 7009Yield 37.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

Triethylamine (8.56 mL, 0.061 mol) and tert-butyl 2-bromoethylcarbamate (see Preparation R above, 11.0 g, 0.049 mol) were added to a solution of 4-{[(2S)-2-hydroxy-3-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-propyl]oxy}benzonitrile (see preparation B above, 12.41 g, 0.038 mol) in DMF (100 mL). The mixture was stirred for 20 h at 40° C., then concentrated in vacuo. The residue was dissolved in chloroform (100 mL), and washed with saturated sodium chloride. The aqueous layer was separated and extracted with chloroform (2×150 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The crude brown oil was chromatographed (×2) on silica gel, eluting first with chloroform:methanol (9:1), then with chloroform:methanol:conc. ammonium hydroxide (9:1:0.05) to afford 4.13 g (24%) of the title compound.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in chloroform (100 mL)
  3. washwashed with saturated sodium chloride
  4. customThe aqueous layer was separated
  5. extractionextracted with chloroform (2×150 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude brown oil was chromatographed (×2) on silica gel
  9. washeluting first with chloroform:methanol (9:1)

Sources & evidence

ORD record
ord-a3a52f6fc8b7487497d6bf9f185a7615
Source dataset
uspto-grants-2010_08
Patent number
US07772229B2

Reaction notes

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