Acetic Acid → (S)-tert-butyl (1-(5-bromo-1H-benzo[d]imidazol-2-yl)-3-oxo-3-(tritylamino)propyl)carbamate

HRID 1424184Notes

Reaction equation

HRID 1424184 reaction equation
[NH:1]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C@H:2]([C:26](O)=O)[CH2:3][C:4](=[O:25])[NH:5][C:6]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[Br:51][C:52]1[CH:53]=[C:54]([NH2:59])[C:55]([NH2:58])=[CH:56][CH:57]=1.C(O)(=O)C>O1CCCC1>[Br:51][C:52]1[CH:57]=[CH:56][C:55]2[NH:58][C:26]([C@@H:2]([NH:1][C:29](=[O:30])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[CH2:3][C:4](=[O:25])[NH:5][C:6]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[N:59][C:54]=2[CH:53]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 3235934-Bromobenzene-1,2-diamineHCID 11385960Boc-Asn(Trt)-OH

Product 1

HCID 178454214(S)-tert-butyl (1-(5-bromo-1H-benzo[d]imidazol-2-yl)-3-oxo-3-(tritylamino)propyl)carbamateYield 99.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Boc-Asn(Trt)-OH (1.05 g, 2.21 mmol) in anhydrous tetrahydrofuran (4 mL) cooled in an ice water bath was added 4-methylmorpholine (0.365 mL, 3.32 mmol) and isobutyl chloroformate (0.316 mL, 2.43 mmol). The reaction mixture was stirred for 1 hour at 0° C. and then 4-bromo-1,2-benzenediamine (414 mg, 2.21 mmol) was added. The reaction mixture was allowed to warm to room temperature over 2 hours and then stirred an additional 2 hours. The reaction mixture was concentrated in vacuo and dried. To the resulting residue was added acetic acid (12 mL, 210 mmol) and the mixture stirred at 65° C. for 2 hours. The reaction was concentrated in vacuo and the residue taken up in ethyl acetate, washed with water, saturated aqueous sodium hydrogen carbonate solution, and brine. The organic layer was dried over anhydrous magnesium sulphate, filtered, and concentrated in vacuo to give crude product that was purified by silica gel column chromatography eluting with a 0-100% ethyl acetate/methylene chloride gradient. This provided the title compound (1.38 g, 61%) as a light tan solid.

Workup

  1. temperatureto warm to room temperature over 2 hours
  2. stirringstirred an additional 2 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customdried
  5. stirringthe mixture stirred at 65° C. for 2 hours
  6. concentrationThe reaction was concentrated in vacuo
  7. washwashed with water, saturated aqueous sodium hydrogen carbonate solution, and brine
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give crude product that
  12. customwas purified by silica gel column chromatography
  13. washeluting with a 0-100% ethyl acetate/methylene chloride gradient

Sources & evidence

ORD record
ord-878fc8edb1ca449d981e476e32e1b0f5
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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