2-Hydroxyisobutyric acid → 2-Hydroxy-1-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-2-methyl-propan-1-one

HRID 708185Notes

Reaction equation

HRID 708185 reaction equation
OC(C(F)(F)F)=O.[NH:8]1[CH2:11][CH:10]([C:12]2[CH:33]=[CH:32][C:15]3[C:16]4[N:17]=[C:18]([C:24]5[N:25]([CH:29]([CH3:31])[CH3:30])[N:26]=[CH:27][N:28]=5)[S:19][C:20]=4[CH2:21][CH2:22][O:23][C:14]=3[CH:13]=2)[CH2:9]1.[OH:34][C:35]([CH3:40])([CH3:39])[C:36](O)=[O:37]>CN(C=O)C>[OH:34][C:35]([CH3:40])([CH3:39])[C:36]([N:8]1[CH2:11][CH:10]([C:12]2[CH:33]=[CH:32][C:15]3[C:16]4[N:17]=[C:18]([C:24]5[N:25]([CH:29]([CH3:31])[CH3:30])[N:26]=[CH:27][N:28]=5)[S:19][C:20]=4[CH2:21][CH2:22][O:23][C:14]=3[CH:13]=2)[CH2:9]1)=[O:37]

Participants

4

Reactant 2

HCID 116712-Hydroxyisobutyric acidHCID 866523168-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt

Product 1

HCID 582038262-Hydroxy-1-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-2-methyl-propan-1-oneYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Following the procedure for 318, 8-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt 235 and 2-hydroxyisobutyric acid were reacted in DMF. Purification by trituration with ether then reverse phase preparative HPLC (Gemini C18 column, gradient 40-98% MeOH in H2O+0.1% HCO2H) gave 444 as a white solid (39 mg, 21%). LCMS: RT=11.04 min, [M+H]+=454. 1H NMR δ (ppm) (CDCl3): 8.36 (1H, d, J=8.19 Hz), 7.90 (1H, s), 7.11 (1H, dd, J=8.22, 1.90 Hz), 7.00-6.96 (1H, m), 5.92-5.83 (1H, m), 4.74 (1H, d, J=9.42 Hz), 4.46 (1H, t, J=9.76 Hz), 4.39 (3H, t, J=5.47 Hz), 4.14 (1H, s), 3.87-3.78 (1H, m), 3.65 (1H, s), 3.40 (2H, t, J=5.00 Hz), 1.60 (6H, d, J=6.63 Hz), 1.43 (6H, s)

Workup

  1. customPurification by trituration with ether

Sources & evidence

ORD record
ord-59dcfb11b0c04c7aa8d07b01e95cd718
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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