1,2-Dimethoxyethane → HCID 69218188, compound

HRID 272765Notes

Reaction equation

HRID 272765 reaction equation
[N:1]1([C:7]2[CH:40]=[CH:39][C:10]([O:11][CH2:12][CH2:13][C:14]3[CH:15]=[CH:16][C:17]4[NH:23][C:22]5[CH:24]=[C:25](B6OC(C)(C)C(C)(C)O6)[CH:26]=[CH:27][C:21]=5[C:20](=[O:37])[NH:19][C:18]=4[CH:38]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[F-].[Cs+].CO[CH2:45][CH2:46]OC>CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:1]1([C:7]2[CH:40]=[CH:39][C:10]([O:11][CH2:12][CH2:13][C:14]3[CH:15]=[CH:16][C:17]4[NH:23][C:22]5[CH:24]=[C:25]([C:46]6[C:45]7[C:17](=[CH:18][N:19]=[CH:20][CH:21]=7)[NH:23][CH:22]=6)[CH:26]=[CH:27][C:21]=5[C:20](=[O:37])[NH:19][C:18]=4[CH:38]=3)=[CH:9][CH:8]=2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 80711,2-DimethoxyethaneHCID 25953Cesium fluorideHCID 59003065HCID 59003065, compound

Product 1

HCID 69218188HCID 69218188, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Procedure

A mixture of Example 695G (53 mg, 0.1 mmol), Example 695K (30 mg, 0.1 mmol), Pd(PPh3)4 (11 mg, 0.01 mmol), and CsF (46 mg, 0.3 mmol) in DME (4 mL) and MeOH (2 mL) was heated under reflux overnight. After the reaction mixture cooled to room temperature, it was partitioned between EtOAc and water. The organic layer was separated, and the aqueous layer was extracted with additional EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified flash column chromatography on silica gel with 100:5:0.5 ethyl acetate/methanol/NH4OH. The desired fractions were collected and concentrated under vacuum, and the residue was further purified by preparative reverse phase HPLC to provide 8 mg of the title compound as a diTFA salt. MS (APCI) m/e 530 (M-H)+, 1H NMR (500 MHz, DMSO-d6): □ 13.30 (s, 1H), 9.78 (s, 1H), 9.26 (s, 1H), 8.71 (d, J=1.87 Hz, 1H), 8.38-8.45 (m, 2H), 7.96 (s, 1H), 7.80 (d, J=8.11 Hz, 1H), 7.47 (d, J=1.56 Hz, 1H), 7.30 (dd, J=8.11, 1.56 Hz, 1H), 6.82-6.96 (m, 7H), 4.05 (t, J=6.86 Hz, 2H), 3.71-3.73 (m, 4H), 2.97-2.99 (m, 4H), 2.87 (t, J=6.55 Hz, 2H).

Workup

  1. temperatureunder reflux overnight
  2. customit was partitioned between EtOAc and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with additional EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified flash column chromatography on silica gel with 100:5:0.5 ethyl acetate/methanol/NH4OH
  10. customThe desired fractions were collected
  11. concentrationconcentrated under vacuum
  12. customthe residue was further purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-e5785c3ea30147abbd08d399b45089be
Source dataset
uspto-grants-2008_11
Patent number
US07456169B2

Reaction notes

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