Methanol → 3,4,5-Trihydroxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid

HRID 1038338Notes

Reaction equation

HRID 1038338 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][CH2:24][C:25]([CH3:63])([C:27]2[O:31][N:30]=[C:29]([NH:32][C:33]([NH:35][C:36]3[CH:41]=[CH:40][C:39]([C:42]4[N:43]=[C:44]5[N:48]([CH:49]=4)[C:47]4[CH:50]=[CH:51][C:52]([O:54][CH2:55][CH2:56][N:57]6[CH2:62][CH2:61][O:60][CH2:59][CH2:58]6)=[CH:53][C:46]=4[S:45]5)=[CH:38][CH:37]=3)=[O:34])[CH:28]=2)[CH3:26])[O:6]1)=[O:4].CO.O.[OH-].[K+]>C(O)(=O)C>[OH:11][CH:10]1[CH:9]([OH:15])[CH:8]([OH:19])[CH:7]([O:23][CH2:24][C:25]([CH3:63])([C:27]2[O:31][N:30]=[C:29]([NH:32][C:33]([NH:35][C:36]3[CH:41]=[CH:40][C:39]([C:42]4[N:43]=[C:44]5[N:48]([CH:49]=4)[C:47]4[CH:50]=[CH:51][C:52]([O:54][CH2:55][CH2:56][N:57]6[CH2:58][CH2:59][O:60][CH2:61][CH2:62]6)=[CH:53][C:46]=4[S:45]5)=[CH:38][CH:37]=3)=[O:34])[CH:28]=2)[CH3:26])[O:6][CH:5]1[C:3]([OH:4])=[O:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 14797Potassium HydroxideHCID 667944213,4,5-Triacetoxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid methyl ester

Product 1

HCID 462144733,4,5-Trihydroxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Final compound 3,4,5-trihydroxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid (I-6) is prepared by following a general procedure given in J. Med. Chem. 1995, 38, 1911). To a stirred mixture of 3,4,5-triacetoxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid methyl ester (1 equivalent) in 4:1 MeOH:water at rt, is added dropwise aq potassium hydroxide (1-4 equivalents) and the mixture is stirred at rt until the reaction is substantially complete as monitored by LCMS or TLC. The mixture is acidified with glacial acetic acid and concentrated under reduced pressure. The residue is purified by preparative reverse-phase HPLC or silica gel flash chromatography to afford 3,4,5-trihydroxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid (I-6).

Workup

  1. customFinal compound 3,4,5-trihydroxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid (I-6) is prepared
  2. concentrationconcentrated under reduced pressure
  3. customThe residue is purified by preparative reverse-phase HPLC or silica gel flash chromatography

Sources & evidence

ORD record
ord-385426165a8b420abba97a245f9409b2
Source dataset
uspto-grants-2013_10
Patent number
US08551963B2

Reaction notes

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