Ethyl 3-bromopropionate → HCID 68467368, compound

HRID 1514238Notes

Reaction equation

HRID 1514238 reaction equation
Cl.[CH3:2][CH:3]([O:5][C:6]1[CH:13]=[CH:12][C:11]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[CH:21][C:22]4[O:28][CH2:27][CH2:26][NH:25][CH2:24][C:23]=4[CH:29]=3)[N:15]=2)=[CH:10][C:7]=1[C:8]#[N:9])[CH3:4].CCN(C(C)C)C(C)C.Br[CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43]>C(#N)C.CCOC(C)=O>[C:8]([C:7]1[CH:10]=[C:11]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[CH:21][C:22]4[O:28][CH2:27][CH2:26][N:25]([CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:24][C:23]=4[CH:29]=3)[N:15]=2)[CH:12]=[CH:13][C:6]=1[O:5][CH:3]([CH3:2])[CH3:4])#[N:9]

Participants

6

Reactant 3

HCID 68320Ethyl 3-bromopropionate3×HCID 81531Diisopropylethylamine3×HCID 68469090HCID 68469090, compound

Product 1

HCID 68467368HCID 68467368, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride (Example 35) (0.101 g, 0.268 mmol) in acetonitrile (2 ml) was added DIPEA (0.094 ml, 0.537 mmol) and ethyl 3-bromopropanoate (0.051 ml, 0.402 mmol). The reaction mixture was stirred and heated at 80° C. under Argon for 6 hours. DIPEA (0.094 ml, 0.537 mmol) and ethyl 3-bromopropanoate (0.051 ml, 0.402 mmol) were added and the reaction stirred and heated at 80° C. under Argon overnight. Additional quantities of DIPEA (0.094 ml, 0.537 mmol) and ethyl 3-bromopropanoate (0.051 ml, 0.402 mmol) were added and the reaction heated again. The reaction mixture was dissolved in EtOAc, washed with saturated NaHCO3 solution (3×15 ml) and water (15 ml), dried (MgSO4) and evaporated. The resulting crude was purified by flash chromatography, eluting with EtOAc/iso-Hexane 10-20% (Biotage Column) to give the title compound (92 mg). MS (ES): C26H28N4O5 requires 476; found 477 [M+H]+.

Workup

  1. stirringthe reaction stirred
  2. temperatureheated at 80° C. under Argon overnight
  3. temperaturethe reaction heated again
  4. washwashed with saturated NaHCO3 solution (3×15 ml) and water (15 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe resulting crude was purified by flash chromatography
  8. washeluting with EtOAc/iso-Hexane 10-20% (Biotage Column)

Sources & evidence

ORD record
ord-709eb887a8824ba1a66905d61eb49f84
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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