HCID 86671455, compound → HCID 68313093, compound

HRID 1530660Notes

Reaction equation

HRID 1530660 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]([CH3:38])([CH2:32]OS(C)(=O)=O)[CH2:25][CH2:26]OS(C)(=O)=O)[CH:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][C:6]([CH3:39])=[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([CH3:38])[CH2:25][CH2:26][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:32]5)=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][C:6]([CH3:39])=[N:5]1)([CH3:3])[CH3:2]

Participants

3

Reactant 1

HCID 86671455HCID 86671455, compound

Product 1

HCID 68313093HCID 68313093, compound

Reagents, catalysts & solvents 1

HCID 6363IsopropylamineSolvent

Procedure

A solution of methanesulfonic acid 3-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]-4-methanesulfonyloxy-3-methylbutyl ester from Example 51 (0.0318 mmol) in isopropylamine (0.7 mL) was heated at 90° C. for 1 h in a sealed vial and then at 130° C. for 2 h using microwave irradiation. After cooling to RT, the crude reaction mixture was 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 affording 261 as a colorless gum (10 mg, 69% over two steps). LCMS: RT 2.80 min [M+H]+ 451.1. 1H NMR (CD3OD, 400 MHz): δ 8.33 (1H, d, J=8.96 Hz), 7.68 (1H, s), 6.75 (1H, dd, J=8.96, 2.51 Hz), 6.60 (1H, d, J=2.49 Hz), 5.93-5.82 (1H, m), 4.49 (4H, s), 3.24 (1H, bd, J=10.84 Hz), 2.99-2.89 (1H, m), 2.76 (1H, bd, J=10.76 Hz), 2.73-2.64 (1H, m), 2.53-2.37 (2H, m), 2.36 (3H, s), 2.11-2.02 (1H, m), 1.60 (3H, s), 1.53 (6H, d, J=6.65 Hz), 1.14 (6H, d, J=6.35 Hz)

Workup

  1. custommicrowave irradiation
  2. customthe crude reaction mixture
  3. customwas purified by column chromatography (C18, gradient 20-50% MeOH in 0.5% TFA/H2O)
  4. washThe cartridge was washed with MeOH
  5. washthe product eluted with 0.5M NH3/MeOH affording 261 as a colorless gum (10 mg, 69% over two steps)

Sources & evidence

ORD record
ord-c0d23668774c4cceb96f26ba99b4a377
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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