HCID 86671480, compound → HCID 68312995, compound

HRID 1530697Notes

Reaction equation

HRID 1530697 reaction equation
[CH:1]1([CH2:4][C:5]([O:18][C:19]2[CH:41]=[CH:40][C:22]3[C:23]4[N:27]([CH2:28][CH2:29][O:30][C:21]=3[CH:20]=2)[CH:26]=[C:25]([C:31]2[N:32]([CH:37]([CH3:39])[CH3:38])[N:33]=[C:34]([CH3:36])[N:35]=2)[N:24]=4)([CH2:12]OS(C)(=O)=O)[CH2:6]OS(C)(=O)=O)[CH2:3][CH2:2]1>C(N)(C)C>[CH:1]1([CH2:4][C:5]2([O:18][C:19]3[CH:41]=[CH:40][C:22]4[C:23]5[N:27]([CH:26]=[C:25]([C:31]6[N:32]([CH:37]([CH3:39])[CH3:38])[N:33]=[C:34]([CH3:36])[N:35]=6)[N:24]=5)[CH2:28][CH2:29][O:30][C:21]=4[CH:20]=3)[CH2:12][N:24]([CH:25]([CH3:31])[CH3:26])[CH2:6]2)[CH2:2][CH2:3]1

Participants

3

Reactant 1

HCID 86671480HCID 86671480, compound

Product 1

HCID 68312995HCID 68312995, compound

Reagents, catalysts & solvents 1

HCID 6363IsopropylamineSolvent

Procedure

A solution of methanesulfonic acid 2-cyclopropylmethyl-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-methanesulfonyloxypropyl ester (87 mg, 0.1427 mmol) in isopropylamine (1.2 mL) was heated at 150° C. for 28 h using microwave irradiation. After cooling to RT, the crude reaction mixture was evaporated and then purified by column chromatography (C18, gradient 25-55% 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 283 as a colourless foam (43.1 mg, 63%). LCMS (Method K): RT 3.15 min [M+H]+ 477.2. 1H NMR (CD3OD, 400 MHz): δ 8.33 (1H, d, J=9.0 Hz), 7.67 (1H, s), 6.57 (1H, dd, J=9.0, 2.6 Hz), 6.36 (1H, d, J=2.5 Hz), 5.87 (1H, septet, J=6.7 Hz), 4.48 (4H, s), 3.72-3.69 (2H, m), 3.38-3.35 (2H, m), 2.49 (1H, septet, J=6.3 Hz), 2.35 (3H, s), 2.04 (2H, d, J=6.6 Hz), 1.52 (6H, d, J=6.6 Hz), 0.99 (6H, d, J=6.3 Hz), 0.80-0.70 (1H, m), 0.45-0.41 (2H, m), 0.03-0.00 (2H, m)

Workup

  1. custommicrowave irradiation
  2. customthe crude reaction mixture
  3. customwas evaporated
  4. custompurified by column chromatography (C18, gradient 25-55% MeOH in 0.5% TFA/H2O)
  5. washThe cartridge was washed with MeOH
  6. washthe product eluted with 0.5M NH3/MeOH affording 283 as a colourless foam (43.1 mg, 63%)
  7. customRT 3.15 min [M+H]+ 477.2

Sources & evidence

ORD record
ord-ece28737419148f58f4b75dca10d3ea0
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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