Hydrochloric Acid → HCID 86681058, compound

HRID 1848069Notes

Reaction equation

HRID 1848069 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([CH2:18][N:19]3[C:23]4=[N:24][CH:25]=[C:26]([C:28]([O:30]C)=[O:29])[CH:27]=[C:22]4[N:21]=[CH:20]3)[CH:15]=[CH:14][C:12]=2[N:13]=1.Cl>C1COCC1.[Li+].[OH-]>[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([CH2:18][N:19]3[C:23]4=[N:24][CH:25]=[C:26]([C:28]([OH:30])=[O:29])[CH:27]=[C:22]4[N:21]=[CH:20]3)[CH:15]=[CH:14][C:12]=2[N:13]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 71550846HCID 71550846, compound

Product 1

HCID 86681058HCID 86681058, compoundYield 18.2%

Reagents, catalysts & solvents 2

HCID 3939Lithium HydroxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carboxylate (210 mg, 0.48 mmol) from Example 79 in THF (5 mL) and 1 M aq LiOH (5 mL) was stirred at rt for 3 h. The reaction mixture was acidified to pH˜1.0 with 2 M aq HCl, and the mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford 3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (37 mg, 18%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 13.15 (br s, 1H), 8.96 (d, J=1.7 Hz, 1H), 8.74 (s, 1H), 8.52 (d, J=1.9 Hz, 1H), 7.98 (d, J=7.3 Hz, 1H), 7.67 (d, J=1.1 Hz, 1H), 7.19-7.33 (m, 2H), 5.53 (s, 2H), 4.75 (br s, 1H), 3.51 (m, 1H), 3.33 (m, 1H), 2.03 (m, 1H), 1.87 (m, 1H), 1.55-1.68 (m, 2H), 1.09-1.35 (m, 4H). LCMS (ESI) m/z 424 (M+H)+.

Workup

  1. customthe mixture was purified directly by reverse-phase
  2. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase

Sources & evidence

ORD record
ord-a3055d5ab301463095b3cca34f587a60
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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