Glycolic 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}-ethanone

HRID 708141Notes

Reaction equation

HRID 708141 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.[C:34](O)(=[O:37])[CH2:35][OH:36]>>[OH:37][CH2:34][C:35]([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:36]

Participants

3

Reactant 2

HCID 757Glycolic 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 582040822-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}-ethanoneYield 27%

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 31 and glycolic acid were reacted. Purification by reverse phase preparative HPLC (Gemini C18 column, gradient 5-98% MeOH in H2O+0.1% HCO2H) gave 397 as a white solid (46 mg, 27%). LCMS: RT=10.33 min, [M+H]+=426. 1H NMR δ (ppm) (DMSO-d6): 8.30 (1H, d, J=8.20 Hz), 8.05 (1H, s), 7.20-7.15 (1H, m), 7.01 (1H, d, J=1.82 Hz), 5.82-5.72 (1H, m), 4.88-4.81 (1H, m), 4.55-4.46 (1H, m), 4.34-4.29 (2H, m), 4.30-4.17 (1H, m), 4.16 (1H, dd, J=9.24, 5.41 Hz), 3.90 (2H, d, J=5.77 Hz), 3.89-3.77 (2H, m), 3.41-3.35 (2H, m), 1.49 (6H, d, J=6.59 Hz)

Workup

  1. customwere reacted
  2. customPurification by reverse phase preparative HPLC (Gemini C18 column, gradient 5-98% MeOH in H2O+0.1% HCO2H)

Sources & evidence

ORD record
ord-818e41fff81f49f4b8948d13f5115083
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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