Lithium hydroxide, monohydrate → HCID 58299865, compound

HRID 875988Notes

Reaction equation

HRID 875988 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[N:21]=[CH:20][C:19]([N:22]5[CH2:27][CH2:26][CH:25]([CH2:28][C:29]([O:31]C)=[O:30])[CH2:24][CH2:23]5)=[CH:18][CH:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:33]=[CH:34][N:35]=[C:36]([F:37])[C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.O.[OH-].[Li+]>O1CCOCC1.CO.O>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[N:21]=[CH:20][C:19]([N:22]5[CH2:27][CH2:26][CH:25]([CH2:28][C:29]([OH:31])=[O:30])[CH2:24][CH2:23]5)=[CH:18][CH:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:33]=[CH:34][N:35]=[C:36]([F:37])[C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 58300113HCID 58300113, compound

Product 1

HCID 58299865HCID 58299865, compoundYield 5.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

Compound 258 (0.100 g, 0.20 mmol) was suspended in dioxane (4.8 mL) and methanol (4.8 mL). A solution of lithium hydroxide, monohydrate (0.0092 g, 0.22 mmol) in 2.0 mL of water was added to the suspension. The reaction was warmed to 70° C. After 1 hour, solvent was removed in vacuo. The residue was dissolved in water (3 mL). Dichloromethane was added (1 mL) and the pH was brought to ca. pH 10 with dilute NaOH. The organics were removed and the aqueous was brought to ca. pH 4 with dilute HCl. The resulting precipitate was filtered. Purification by RP-HPLC on C18 column (10-90% CH3CN in water with 0.1% TFA) provided compound 259 (5 mg) as a TFA salt. 1H NMR (500 MHz, DMSO-d6) δ 1.28-1.41 (m, J=12.17, 12.01, 12.01, 3.18 Hz, 2 H) 1.68-1.94 (m, 5 H) 1.99-2.09 (m, 2 H) 2.09-2.19 (m, 2 H) 2.21-2.34 (m, 4 H) 2.81 (t, J=11.49 Hz, 2 H) 3.71 (d, J=12.23 Hz, 2 H) 5.53 (quin, J=9.11 Hz, 1 H) 7.72 (d, J=9.05 Hz, 1 H) 7.98 (br. s., 1 H) 8.06 (d, J=8.56 Hz, 1 H) 8.11-8.18 (m, 1 H) 8.25 (dd, J=4.65, 2.93 Hz, 1 H) 9.51 (s, 1 H) 11.43 (br. s., 1 H) ppm. LCMS-ESI (POS), M/Z, M+1: Found 490.1, Calculated 490.2.

Workup

  1. customsolvent was removed in vacuo
  2. dissolutionThe residue was dissolved in water (3 mL)
  3. additionDichloromethane was added (1 mL)
  4. customThe organics were removed
  5. filtrationThe resulting precipitate was filtered
  6. customPurification by RP-HPLC on C18 column (10-90% CH3CN in water with 0.1% TFA)

Sources & evidence

ORD record
ord-9fabd21084314371b3bc86b69d9566db
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

Loading…