Lithium hydroxide, monohydrate → HCID 90281476, compound

HRID 1471653Notes

Reaction equation

HRID 1471653 reaction equation
[Br:1][C:2]1[N:10](C(OC(C)(C)C)=O)[C:9]2[C:4](=[N:5][C:6]([O:18][CH3:19])=[CH:7][CH:8]=2)[C:3]=1[CH2:20][C:21]([O:23]CC)=[O:22].O[Li].O>C1COCC1.CO.O>[Br:1][C:2]1[NH:10][C:9]2[C:4](=[N:5][C:6]([O:18][CH3:19])=[CH:7][CH:8]=2)[C:3]=1[CH2:20][C:21]([OH:23])=[O:22]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 90167983HCID 90167983, compound

Product 1

HCID 90281476HCID 90281476, compoundYield 85.7%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

tert-Butyl 2-bromo-3-(2-ethoxy-2-oxoethyl)-5-methoxy-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (380 mg, 0.9 mmol) was dissolved in 12 mL of THF/MeOH/H2O (3/2/1) and to it was added LiOH.H2O (116 mg, 2.7 mmol). The reaction mixture was allowed to stir at ambient temperature for 3 hours and then purified by RP HPLC eluting with acetonitrile/water to afford 220 mg of 2-(2-bromo-5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)acetic acid. Dissolved 200 mg of the above acid (0.7 mmol) and (S)-methyl 3-(3-allylphenyl)-2-aminopropanoate hydrochloride (197 mg, 0.77 mmol) in 5 mL of DMF and to it was added N,N-diisopropylethylamine (366 μL, 2.1 mmol). The reaction mixture was cooled down to 0° C. and to it was added HATU (319 mg, 8.4 mmol), and then it was allowed to stir at ambient temperature for 20 minutes. The reaction mixture was purified by RP HPLC eluting with acetonitrile/water (with 0.1% TFA) to afford 210 mg (0.43 mmol) of (S)-methyl 3-(3-allylphenyl)-2-(2-(2-bromo-5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)acetamido)propanoate which was dissolved in 5 mL of CH2Cl2 and cooled down to 0° C. To it were added N,N-diisopropylethylamine (0.15 mL, 0.86 mmol), di-tert-butyl carbonate (113 mg, 0.86 mmol) and 4-dimethylaminopyridine (5.2 mg, 0.04 mmol). The resulting mixture was allowed to stir for 5 minutes and then partitioned between ethyl acetate and water. The organic layer was separated and washed with brine, dried over MgSO4, filtered and the filtrate was concentrated to dryness. It was purified by silica gel chromatography eluting with EtOAc/hexanes) to afford 230 mg of (S)-tert-butyl 3-(2-(3-(3-allylphenyl)-1-methoxy-1-oxopropan-2-ylamino)-2-oxoethyl)-2-bromo-5-methoxy-1H-pyrrolo[3,2-b]pyridine-1-carboxylate MS (m/z): 586.0 [M+H]+; HPLC retention time 4.86 min (5-99% acetonitrile:water with 0.05% formic acid).

Workup

  1. custompurified by RP HPLC
  2. washeluting with acetonitrile/water

Sources & evidence

ORD record
ord-7fe7e0ad531140ddaf8e02df831f18be
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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