4-methyl-5-(oxiran-2-yl)isobenzofuran-1(3H)-one → 5-fluoro-1-({4-[2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}methyl)-2,3-dihydro-1H-indene-4-carbonitrile

HRID 1187149Notes

Reaction equation

HRID 1187149 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]2[CH:7]([CH2:11][N:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:6][CH2:5][C:4]=2[C:3]=1[C:18]#[N:19].[CH3:20][C:21]1[C:29]2[CH2:28][O:27][C:26](=[O:30])[C:25]=2[CH:24]=[CH:23][C:22]=1[CH:31]1[CH2:33][O:32]1>CCO>[F:1][C:2]1[CH:10]=[CH:9][C:8]2[CH:7]([CH2:11][N:12]3[CH2:13][CH2:14][N:15]([CH2:33][CH:31]([OH:32])[C:22]4[CH:23]=[CH:24][C:25]5[C:26](=[O:30])[O:27][CH2:28][C:29]=5[C:21]=4[CH3:20])[CH2:16][CH2:17]3)[CH2:6][CH2:5][C:4]=2[C:3]=1[C:18]#[N:19]

Participants

4

Reactant 2

HCID 552705554-methyl-5-(oxiran-2-yl)isobenzofuran-1(3H)-oneHCID 595686755-fluoro-1-(piperazin-1-ylmethyl)-2,3-dihydro-1H-indene-4-carbonitrile

Product 1

HCID 498019355-fluoro-1-({4-[2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}methyl)-2,3-dihydro-1H-indene-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

5-Fluoro-1-(piperazin-1-ylmethyl)-2,3-dihydro-1H-indene-4-carbonitrile (60 mg, 0.23 mmol), 4-methyl-5-oxiran-2-yl-2-benzofuran-1(3H)-one (88 mg, 0.46 mmol), were added to a 5 mL microwave tube containing a stir bar; to the mixture was added EtOH (2.5 mL). The tube was capped, degassed and purged with N2. It was then placed in a microwave reactor and heated at 120° C. for 1 hour; LC indicated formation of some desired product. The tube was again placed in a microwave reactor and heated again at 150° C. for 30 min; LC indicated formation of more product. The solution was concentrated to dryness, re-dissolved in DCM (20 mL) and was then absorbed into silica gel. It was then loaded onto a silica column for separation with the solvent system of (10% MeOH in DCM), to give 5-fluoro-1-({4-[2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}methyl)-2,3-dihydro-1H-indene-4-carbonitrile. LC-MS (IE, m/z): 450 [M+1]+.

Workup

  1. additioncontaining a stir bar
  2. customThe tube was capped
  3. customdegassed
  4. custompurged with N2
  5. customIt was then placed in a microwave reactor
  6. customThe tube was again placed in a microwave reactor
  7. temperatureheated again at 150° C. for 30 min
  8. concentrationThe solution was concentrated to dryness
  9. dissolutionre-dissolved in DCM (20 mL)
  10. customwas then absorbed into silica gel
  11. customIt was then loaded onto a silica column for separation with the solvent system of (10% MeOH in DCM)

Sources & evidence

ORD record
ord-9356bc23204540cabbbfc9dbce65421a
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

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