Lithium hydroxide, monohydrate → HCID 72950193, compound

HRID 1526771Notes

Reaction equation

HRID 1526771 reaction equation
[Br:1][C:2]1[C:3]([OH:41])=[C:4]([C@@H:12]([NH:19][C:20](=[O:40])[CH2:21][NH:22][C:23](=[O:39])[C:24]2[CH:29]=[C:28]([NH:30][C:31]3[NH:32][CH2:33][CH:34]([OH:37])[CH2:35][N:36]=3)[CH:27]=[C:26]([OH:38])[CH:25]=2)[CH2:13][C:14]([O:16]CC)=[O:15])[CH:5]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:7]=1.C(#N)C.O.O.[OH-].[Li+]>O.C(#N)C>[Br:1][C:2]1[C:3]([OH:41])=[C:4]([C@@H:12]([NH:19][C:20](=[O:40])[CH2:21][NH:22][C:23](=[O:39])[C:24]2[CH:29]=[C:28]([NH:30][C:31]3[NH:36][CH2:35][CH:34]([OH:37])[CH2:33][N:32]=3)[CH:27]=[C:26]([OH:38])[CH:25]=2)[CH2:13][C:14]([OH:16])=[O:15])[CH:5]=[C:6]([C:8]([CH3:9])([CH3:10])[CH3:11])[CH:7]=1

Participants

6

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 18373917Acetonitrile--water (1/1)HCID 86709939HCID 86709939, compound

Product 1

HCID 72950193HCID 72950193, compoundYield 58.6%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6342AcetonitrileSolvent

Procedure

To a suspension of crude (3S)-ethyl 3-(3-bromo-5-(tert-butyl)-2-hydroxyphenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoate (1.389 g, 2.19 mmol) in a 1:1 mixture of acetonitrile/water (10.0 mL) was added lithium hydroxide monohydrate (0.735 g, 17.51 mmol) at room temperature and the reaction mixture was stirred at room temperature for 3 h to afford a pale yellow solution. Acetonitrile was evaporated on a rotary evaporator to give a pale yellow aqueous residue. The residue was extracted with dichloromethane (2×25 mL) to remove HOBt and DIPU. The aqueous layer was neutralized with TFA (3.0 mL in 5.0 mL CH3CN) and the mixture was evaporated in vacuo to give a pale viscous residue. The crude product was purified by reverse-phase HPLC on Biotage SP1 system using a gradient 10-40% CH3CN in water containing 0.05% TFA to afford a colorless glassy solid. The purified product was dissolved in water containing a few drops of acetonitrile and lyophilized to afford a colorless powder (778.0 mg). LC/MS analysis of the purified product shows the desired product's mass: m/z 606 (79BrM+H) and m/z 608 (81BrM+H), Calc'd for C26H32BrN5O7: 606.466. 1H NMR (400 MHz, DMSO-d6): δ 1.25 (s, 9H, (CH3)3C—), 2.70 (ABq, JAB=16.00 and 8.73 Hz and JAB=15.95 and 5.45 Hz, 2H, —CH2—COOH), 3.17 (d, J=12.0 Hz, 2H), 3.35 (d, J=11.0 Hz, 2H), 3.89 (d, J=6.0 Hz, 2H), 4.09 (M, 1H), 5.45 (brm, 1H, —NH—CH—CH2—COOH), 6.75 (brt/m, J=2.02 Hz, 1H), 7.13 (dt, 2H), 7.26 (d, J=2.30 Hz, 1H), 7.34 (d, J=2.32 Hz, 1H), 8.60 (d, J=8.26 Hz, 1H), 8.64 (t, J=5.85 Hz, 1H), 9.31 (s, 1H), 9.60 (s, 1H), 10.02 (brs, 1H), 12.27 (brs, 1H, —COOH). 1H NMR spectrum of the sample was consistent with the suggested structure of the product.

Workup

  1. customto afford a pale yellow solution
  2. customAcetonitrile was evaporated on a rotary evaporator
  3. customto give a pale yellow aqueous residue
  4. extractionThe residue was extracted with dichloromethane (2×25 mL)
  5. customto remove HOBt and DIPU
  6. customthe mixture was evaporated in vacuo
  7. customto give a pale viscous residue
  8. customThe crude product was purified by reverse-phase HPLC on Biotage SP1 system
  9. customto afford a colorless glassy solid

Sources & evidence

ORD record
ord-e1163e5051944f42b9a7261c306ff6d3
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

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