HCID 86671479, compound → HCID 68312942, compound

HRID 1530691Notes

Reaction equation

HRID 1530691 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([O:23][C:24]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)([CH2:31]OS(C)(=O)=O)[CH2:25]OS(C)(=O)=O)[CH:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][C:6]([CH3:43])=[N:5]1)([CH3:3])[CH3:2]>C(N)(C)C>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[CH:20][C:21]([O:23][C:24]5([C:37]6[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=6)[CH2:31][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:25]5)=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][C:6]([CH3:43])=[N:5]1)([CH3:2])[CH3:3]

Participants

3

Reactant 1

HCID 86671479HCID 86671479, compound

Product 1

HCID 68312942HCID 68312942, compoundYield 71.4%

Reagents, catalysts & solvents 1

HCID 6363IsopropylamineSolvent

Procedure

A solution of methanesulfonic acid 2-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]-3-methanesulfonyloxy-2-phenylpropylester (41.5 mg, 0.0657 mmol) in isopropylamine (0.7 mL) was heated at 140° C. for 12 h using microwave irradiation. After cooling to RT, the crude reaction mixture was evaporated and then purified by column chromatography (C18, gradient 20-50% MeOH in 0.5% TFA/H2O) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3/MeOH. Further purification by column chromatography (Si-PCC, gradient 2-10% MeOH in DCM) affording 275 as a colourless gum (11.7 mg, 36%). LCMS (Method K): RT 3.17 min [M+H]+ 499.1. 1H NMR (CD3OD, 400 MHz): δ 8.22 (1H, d, J=9.0 Hz), 7.62 (1H, s), 7.59-7.57 (2H, m), 7.40-7.36 (2H, m), 7.31-7.27 (1H, m), 6.47 (1H, dd, J=9.0, 2.5 Hz), 6.21 (1H, d, J=2.5 Hz), 5.82 (1H, septet, J=6.7 Hz), 4.43-4.38 (4H, m), 3.88 (2H, d, J=9.2 Hz), 3.67 (2H, d, J=9.2 Hz), 2.58 (1H, septet, J=6.2 Hz), 2.34 (3H, s), 1.49 (6H, d, J=6.7 Hz), 1.02 (6H, d, J=6.2 Hz)

Workup

  1. custommicrowave irradiation
  2. customthe crude reaction mixture
  3. customwas evaporated
  4. custompurified by column chromatography (C18, gradient 20-50% MeOH in 0.5% TFA/H2O)
  5. washThe cartridge was washed with MeOH
  6. washthe product eluted with 0.5M NH3/MeOH
  7. customFurther purification by column chromatography (Si-PCC, gradient 2-10% MeOH in DCM)

Sources & evidence

ORD record
ord-390ca4ef1bed4377af78ea475955cc17
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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