Divinyl sulfone → HCID 58204487, compound

HRID 1498247Notes

Reaction equation

HRID 1498247 reaction equation
Cl.[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[N:10]1[C:14]([N:15]2[N:24]=[C:23]3[C:17]([CH2:18][CH2:19][O:20][C:21]4[CH:28]=[CH:27][C:26]([C:29]5([CH2:35][OH:36])[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]5)=[CH:25][C:22]=43)=[CH:16]2)=[N:13][CH:12]=[N:11]1.CCN(C(C)C)C(C)C.[CH:46]([S:48]([CH:51]=C)(=[O:50])=[O:49])=[CH2:47]>>[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[N:10]1[C:14]([N:15]2[N:24]=[C:23]3[C:17]([CH2:18][CH2:19][O:20][C:21]4[CH:28]=[CH:27][C:26]([C:29]5([CH2:35][OH:36])[CH2:30][CH2:31][N:32]([CH2:47][CH2:46][S:48]([CH3:51])(=[O:50])=[O:49])[CH2:33][CH2:34]5)=[CH:25][C:22]=43)=[CH:16]2)=[N:13][CH:12]=[N:11]1

Participants

4

Reactant 3

HCID 6496Divinyl sulfoneHCID 81531DiisopropylethylamineHCID 67050654HCID 67050654, compound

Product 1

HCID 58204487HCID 58204487, compoundYield 57.5%

Procedure

To a stirring mixture of (4-{2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-2H-6-oxa-1,2-diaza-benzo[e]azulen-9-yl}-piperidin-4-yl)-methanol hydrochloride 75 (97 mg, 0.1873 mmol) in IMS (3 mL) was added DIPEA (165 L, 0.94 mmol) followed by vinyl sulfone (18 ul, 0.206 mmol) at RT, as illustrated in FIG. 16. After 3 h the solvent was removed in vacuo and the residue was subjected to HPLC (Gemini C6-Phenyl column, gradient 10 to 60%, 20 min ramp) to afford 188 (63 mg, 53%). 1H NMR δ ppm (DMSO-d6): 8.42-8.39 (1 H, m), 8.23 (1 H, s), 8.19 (1 H, s), 7.80 (1 H, td, J=8.77, 5.87 Hz), 7.53 (1 H, ddd, J=10.34, 8.85, 2.77 Hz), 7.36 (1 H, d, J=2.40 Hz), 7.33-7.27 (1 H, m), 7.12 (1 H, dd, J=8.59, 2.48 Hz), 6.85 (1 H, dd, J=8.55, 4.83 Hz), 4.17 (2 H, t, J=5.04 Hz), 3.22-3.14 (6 H, m), 3.02 (2 H, t, J=5.09 Hz), 2.98 (3 H, s), 2.02 (2 H, s), 1.72 (4 H, s). 2 Protons obscured by water peak. LCMS: RT=6.57 min, M+H+=585

Workup

  1. customAfter 3 h the solvent was removed in vacuo
  2. customwas subjected to HPLC (Gemini C6-Phenyl column, gradient 10 to 60%, 20 min ramp)

Sources & evidence

ORD record
ord-4e9ad9d9eb88453faad49921d72bcd80
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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