Methanol → HCID 68876619, compound

HRID 1781994Notes

Reaction equation

HRID 1781994 reaction equation
C[O:2][C:3]([CH:5]1[CH:10]([O:11]C(=O)C)[CH:9]([O:15]C(=O)C)[CH:8]([O:19]C(=O)C)[CH:7]([O:23][C:24](=[O:49])[NH:25][CH2:26][CH2:27][C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([S:37]([C:40]3[N:47]4[C:43]([S:44][CH:45]=[CH:46]4)=[N:42][C:41]=3[Cl:48])(=[O:39])=[O:38])[CH:29]=2)[O:6]1)=[O:4].CO.O[Li].O>C1COCC1.O>[Cl:48][C:41]1[N:42]=[C:43]2[N:47]([C:40]=1[S:37]([N:30]1[C:31]3[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:28]([CH2:27][CH2:26][NH:25][C:24]([O:23][C@@H:7]3[O:6][C@H:5]([C:3]([OH:4])=[O:2])[C@@H:10]([OH:11])[C@H:9]([OH:15])[C@H:8]3[OH:19])=[O:49])=[CH:29]1)(=[O:38])=[O:39])[CH:46]=[CH:45][S:44]2

Participants

6

Reactant 3

HCID 887MethanolHCID 168937Lithium hydroxide, monohydrateHCID 57587918HCID 57587918, compound

Product 1

HCID 68876619HCID 68876619, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3,4,5-triacetoxy-6-(2-{1-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)sulfonyl]-1H-indol-3-yl}ethycarbamoyloxy)tetrahydropyran-2-carboxylic acid methyl ester (1.0 g, 1.35 mmol) in THF is treated with CH3OH (38.8 mL) and H2O (10 mL), cooled to 0° C. (ice-water bath), treated with a solution of LiOH.H2O (340 mg, 8.1 mmol, 6 eq) in H2O (5.5 mL) [0.1 N LiOH/MeOH/THF/H2O] and stirred at 0° C. for 2 h under N2 atmosphere. Progress of the deprotection is monitored via reversed-phase TLC (SiO2—C18 MeCN/H2O, 3/7). The reaction mixture is diluted with 150 mL of H2O, neutralized by the addition of 10 g of amberlite-120 (plus) cation exchange material (H+ form) and filtered. The filtrate is concentrated under reduced pressure to an aqueous suspension. This suspension is freeze dried and lyophilized to give the title product, 700 mg (86% yield). Further purification by silica gel column chromatography [CHCl3/CH3OH/H2O (7:3:0.5) as a eluent] provides the title product, 310 mg, 98% pure, identified by mass spectral and NMR analyses. 1H NMR (300 MHz, DMSO-d6): 8.31 (d, 1H, J=4.5 Hz), 7.94-7.91 (m, 1H), 7.82 (s, 1H), 7.69 (d, 1H, J=4.2 Hz), 7.64-7.57 (m, 2H), 7.39-7.27 (m, 2H), 5.31 (d, 1H, J=8.1 Hz), 3.69 (d, 1H, J=9.0 Hz), 3.37-3.13 (m, 5H), 2.82 (t, 2H, J=7.0 Hz); 13C (75 MHz, DMSO-d6): 170.6, 155.4, 155.3, 152.3, 139.2, 134.9, 131.6, 125.7, 124.5, 124.4, 121.1, 121.1, 120.7, 118.8, 116.6, 113.8, 95.5, 76.6, 76.5, 72.8, 72.0, 25.2; LC/MS (ESI) retention time=35.12, [M+H]+=600.7.

Workup

  1. additionneutralized by the addition of 10 g of amberlite-120 (plus) cation exchange material (H+ form)
  2. filtrationfiltered
  3. concentrationThe filtrate is concentrated under reduced pressure to an aqueous suspension
  4. customdried

Sources & evidence

ORD record
ord-9adc3242043549e2b147b75100f9d183
Source dataset
uspto-grants-2009_03
Patent number
US07498327B2

Reaction notes

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