Triethylamine → tert-Butyl 2-{7-[3-(4-cyanoanilino)propyl]-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl}ethylcarbamate

HRID 500504Notes

Reaction equation

HRID 500504 reaction equation
Br[CH2:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[CH:12]12[O:20][CH:16]([CH2:17][NH:18][CH2:19]1)[CH2:15][N:14]([CH2:21][CH2:22][CH2:23][NH:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=1)[CH2:13]2.C(N(CC)CC)C>CN(C=O)C>[NH4+:4].[OH-:6].[C:29]([C:28]1[CH:27]=[CH:26][C:25]([NH:24][CH2:23][CH2:22][CH2:21][N:14]2[CH2:15][CH:16]3[O:20][CH:12]([CH2:19][N:18]([CH2:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[CH2:17]3)[CH2:13]2)=[CH:32][CH:31]=1)#[N:30]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 185403854-{[3-(9-Oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]amino}benzonitrile

Product 2

HCID 14923Ammonium HydroxideHCID 9888884tert-Butyl 2-{7-[3-(4-cyanoanilino)propyl]-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl}ethylcarbamateYield 91.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of tert-butyl 2-bromoethylcarbamate (4.21 g, 0.019 mol; see Preparation R above) in DMF (65 mL) was added 4-{[3-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]amino}benzonitrile (see Preparation C above, 4.48 g, 0.016 mol) and triethylamine (3.27 mL, 0.024 mol). The mixture was stirred overnight at 35° C. and then concentrated in vacuo. The residue was dissolved in dichloromethane (80 mL) and washed with saturated sodium chloride. The aqueous layer was extracted with dichloromethane (1×150 mL). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The crude red-brown oil was chromatographed (×2) on silica gel eluting with chloroform:methanol:conc. NH4OH (9:1:0.02) to afford 3.75 g (56%) of the title compound.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (80 mL)
  3. washwashed with saturated sodium chloride
  4. extractionThe aqueous layer was extracted with dichloromethane (1×150 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude red-brown oil was chromatographed (×2) on silica gel eluting with chloroform

Sources & evidence

ORD record
ord-1b51881f0a3e4ff793c665f0c0fa0d79
Source dataset
uspto-grants-2010_08
Patent number
US07772229B2

Reaction notes

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