Cesium carbonate → HCID 69591796, compound

HRID 1795936Notes

Reaction equation

HRID 1795936 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1)[CH:12]([C:15]1[NH:20][C:19](=[O:21])[C:18]2=[CH:22][CH:23]=[CH:24][N:17]2[N:16]=1)[CH2:13][CH3:14])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[F:41][C:42]1[CH:49]=[CH:48][C:45]([CH2:46]Br)=[CH:44][CH:43]=1>O1CCOCC1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:34])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([CH:12]([C:15]1[N:20]([CH2:46][C:45]2[CH:48]=[CH:49][C:42]([F:41])=[CH:43][CH:44]=2)[C:19](=[O:21])[C:18]2=[CH:22][CH:23]=[CH:24][N:17]2[N:16]=1)[CH2:13][CH3:14])[C:25](=[O:33])[C:26]1[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 680214-Fluorobenzyl bromideHCID 136411691(+/-)-(3-{(4-Methylbenzoyl)-[1-(4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4] triazin-2-yl)-propyl]amino}propyl)carbamic acid tert-butyl ester

Product 1

HCID 69591796HCID 69591796, compoundYield 15.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of (±)-(3-{(4-methylbenzoyl)-[1-(4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4] triazin-2-yl)-propyl]-amino}-propyl)-carbamic acid tert-butyl ester (Example 3 A, 38 mg, 0.08 mmol) and cesium carbonate (40 mg, 0.12 mmol) in dioxane (1 mL) was stirred at 40° C., under Ar, for 45 min. To the mixture was added 4-fluorobenzyl bromide (22 mg, 0.12 mmol) and the reaction mixture was stirred at 40° C. for 24 h before being diluted with ethyl acetate. The ethyl acetate layer was washed twice with water and once with brine, before being dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude product was purified by preparative HPLC (YMC S10 ODS, 30×500 mm, 30 minute gradient from 74–90% aqueous methanol with 0.1% TFA). The appropriate fractions were combined, neutralized with saturated aqueous sodium bicarbonate, and then concentrated in vacuo to remove methanol. The mixture was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed once each with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to yield the title compound (7 mg, 15%): 1H NMR (CDCl3) δ 7.44–6.99 (m, 10H), 6.61 (m, 1H), 5.91 (m, 1H), 5.88 (m, 1H), 4.83 (m, 1H), 3.86 (m, 1H), 3.33 (m, 2H), 2.71 (m, 2H), 2.39 (s, 3H), 2.05 (m, 1H), 1.85 (m, 1H), 1.62 (m, 2H), 1.39 (s, 9H), 0.71 (m, 3H); MS (ESI+), 576.17 (M++H).

Workup

  1. stirringthe reaction mixture was stirred at 40° C. for 24 h
  2. washThe ethyl acetate layer was washed twice with water and once with brine
  3. dry with materialbefore being dried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by preparative HPLC (YMC S10 ODS, 30×500 mm, 30 minute gradient from 74–90% aqueous methanol with 0.1% TFA)
  6. concentrationconcentrated in vacuo
  7. customto remove methanol
  8. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
  9. washThe combined organic layers were washed once each with water and brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-220b0da483b3472aaaf540a40d5b32a8
Source dataset
uspto-grants-2006_04
Patent number
US07030118B2

Reaction notes

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