Cesium carbonate → Methyl 3-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinyl]propanoate formic acid salt

HRID 2059927Notes

Reaction equation

HRID 2059927 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:12]=[CH:11][C:10]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[CH2:20][CH2:21][NH:22][CH2:23]4)[N:14]=2)=[CH:9][C:6]=1[C:7]#[N:8])[CH3:3].Br[CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH:31]([OH:33])=[O:32].[C:7]([C:6]1[CH:9]=[C:10]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[CH2:20][CH2:21][N:22]([CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])[CH2:23]4)[N:14]=2)[CH:11]=[CH:12][C:5]=1[O:4][CH:2]([CH3:1])[CH3:3])#[N:8]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 76934Methyl 3-bromopropanoate2×HCID 441248992-[(1-Methylethyl)oxy]-5-[3-(1,2,3,4-tetrahydro-5-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile

Product 1

HCID 68498188Methyl 3-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinyl]propanoate formic acid salt

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 2-[(1-methylethyl)oxy]-5-[3-(1,2,3,4-tetrahydro-5-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile (Example 3, 28.8 mg, 0.080 mmol), methyl 3-bromopropionate (35 μl, 0.32 mmol) and Cs2CO3 (130 mg, 0.40 mmol) in DMF (2 mL) was stirred at room temperature for 1 h, and then irradiated to 60° C. for 5 min in the microwave. More methyl 3-bromopropionate (35 μl, 0.32 mmol) was added and the suspension was stirred at room temperature for 3.5 h, and then irradiated to increasing temperatures in the microwave until 150° C. for 30 min was achieved. The suspension was filtered and concentrated in vacuo then purified by MDAP to give the title compound as a yellow film (5.9 mg, 17%). 1H NMR (400 MHz, CDCl3) δ 8.42 (1H, d), 8.33 (1H, dd), 8.21 (1H, br. s), 8.04 (1H, d), 7.35 (1H, t), 7.24 (1H, d), 7.13 (1H, d), 4.80 (1H, sept), 3.99 (2H, s), 3.72 (3H, s), 3.38 (2H, t), 3.12-3.06 (4H, m), 2.78 (2H, t), 1.48 (6H, d); m/z (ES) 447 [M+H]+.

Workup

  1. customirradiated to 60° C. for 5 min in the microwave
  2. stirringthe suspension was stirred at room temperature for 3.5 h
  3. customirradiated
  4. temperatureto increasing temperatures in the microwave until 150° C. for 30 min
  5. filtrationThe suspension was filtered
  6. concentrationconcentrated in vacuo
  7. customthen purified by MDAP

Sources & evidence

ORD record
ord-171be327a7b5428f82c10ba3e35f0eb1
Source dataset
uspto-grants-2012_10
Patent number
US08278324B2

Reaction notes

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