Benzylamine → HCID 11642732, compound

HRID 1993984Notes

Reaction equation

HRID 1993984 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:21][CH2:20][C@H:19]([CH2:22]O)[C@@H:18]([CH2:24]O)[C@@H:17]2[C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=2[CH3:33])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH2:48]([NH2:55])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:48]([N:55]1[CH2:24][C@H:18]2[C@H:17]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=3[CH3:33])[C@@H:16]([O:15][C@@H:13]([C:5]3[CH:4]=[C:3]([C:2]([F:1])([F:34])[F:35])[CH:8]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:6]=3)[CH3:14])[O:21][CH2:20][C@@H:19]2[CH2:22]1)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86620051HCID 86620051, compound

Product 1

HCID 11642732HCID 11642732, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The intermediate from step I (2.44 g, 4.87 mmol) was combined with DMAP (0.15 g, 1.2 mmol) and dissolved in 38 mL DCM. The reaction vessel was cooled 0° C. followed by the sequential addition of triethylamine (2.72 mL, 19.5 mmol) and methanesulfonyl chloride (0.95 mL, 12.2 mmol). After 5 minutes, the reaction vessel was warmed to ambient temperature where it remained for 0.5 hr. The reaction was quenched by the addition of a saturated solution of NaHCO3. The aqueous mixture was extracted several times with DCM. The combined organic extracts were washed with 1 M HCl, brine, dried over Na2SO4, filtered through a fritted funnel and concentrated in vacuo. The crude bis-mesylate was dissolved in 50 mL n-butanol followed by the addition of benzylamine (3.19 mL, 29.2 mmol). The reaction vessel was heated to 100° C. for 3.5 hr. The volatiles were removed in vacuo and the crude residue was purified on silica gel and eluted with a combination of EtOAc/hexanes (35-95% EtOAc/hexanes linear gradient) which furnished the title compound. MS: (MH)+582.

Workup

  1. temperaturethe reaction vessel was warmed to ambient temperature where it
  2. waitremained for 0.5 hr
  3. customThe reaction was quenched by the addition of a saturated solution of NaHCO3
  4. extractionThe aqueous mixture was extracted several times with DCM
  5. washThe combined organic extracts were washed with 1 M HCl, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered through a fritted funnel
  8. concentrationconcentrated in vacuo
  9. dissolutionThe crude bis-mesylate was dissolved in 50 mL n-butanol
  10. temperatureThe reaction vessel was heated to 100° C. for 3.5 hr
  11. customThe volatiles were removed in vacuo
  12. customthe crude residue was purified on silica gel
  13. washeluted with a combination of EtOAc/hexanes (35-95% EtOAc/hexanes linear gradient) which

Sources & evidence

ORD record
ord-9b7e8338d5bb4955949095e72b0d376a
Source dataset
uspto-grants-2010_01
Patent number
US07652058B2

Reaction notes

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