HCID 86671482, compound → HCID 68312760, compound

HRID 1530712Notes

Reaction equation

HRID 1530712 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]([CH2:35]OS(C)(=O)=O)([CH2:31][CH:32]([CH3:34])[CH3:33])[CH2:25]OS(C)(=O)=O)[CH:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][C:6]([CH3:41])=[N:5]1)([CH3:3])[CH3:2]>C(N)(C)C>[CH2:31]([C:24]1([O:23][C:21]2[CH:20]=[CH:19][C:16]3[C:17]4[N:11]([CH:10]=[C:9]([C:8]5[N:4]([CH:1]([CH3:2])[CH3:3])[N:5]=[C:6]([CH3:41])[N:7]=5)[N:18]=4)[CH2:12][CH2:13][O:14][C:15]=3[CH:22]=2)[CH2:25][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:35]1)[CH:32]([CH3:33])[CH3:34]

Participants

3

Reactant 1

HCID 86671482HCID 86671482, compound

Product 1

HCID 68312760HCID 68312760, compound

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]-2-methanesulfonyloxymethyl-4-methylpentyl ester (194 mmol) in isopropylamine (2 mL) was heated at 150° C. for 33 h using microwave irradiation. After cooling to RT, the crude reaction mixture was evaporated and then purified by column chromatography (C18, gradient 30-55% 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 301 as a colourless foam (95 mg, 100% over 2 steps). LCMS (Method K): RT 3.29 min [M+H]+ 479.2. 1H NMR (CD3OD, 400 MHz): δ 8.41 (1H, d, J=9.0 Hz), 7.69 (1H, s), 6.67 (1H, bd, J=9.0 Hz), 6.51 (1H, bs), 5.84 (1H, septet, J=6.6 Hz), 4.51 (4H, s), 4.44-4.37 (4H, m), 3.49-3.42 (1H, m), 2.36 (3H, s), 2.17 (2H, d, J=6.9 Hz), 1.72 (1H, nonet, J=6.8 Hz), 1.52 (6H, d, J=6.6 Hz), 1.25 (6H, d, J=6.5 Hz), 0.92 (6H, d, J=6.8 Hz)

Workup

  1. custommicrowave irradiation
  2. customthe crude reaction mixture
  3. customwas evaporated
  4. custompurified by column chromatography (C18, gradient 30-55% MeOH in 0.5% TFA/H2O)
  5. washThe cartridge was washed with MeOH
  6. washthe product eluted with 0.5M NH3/MeOH affording 301 as a colourless foam (95 mg, 100% over 2 steps)
  7. customRT 3.29 min [M+H]+ 479.2

Sources & evidence

ORD record
ord-40617f4c078842d3b091823b95e67a16
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

Loading…