Acetic Acid → HCID 178442068, compound

HRID 1424186Notes

Reaction equation

HRID 1424186 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.[CH2:51]([C:56]1[CH:57]=[C:58]([NH2:63])[C:59]([NH2:62])=[CH:60][CH:61]=1)[C:52]([CH3:55])([CH3:54])[CH3:53].C(O)(=O)C>C(#N)C>[CH2:51]([C:56]1[CH:61]=[CH:60][C:59]2[NH:62][C:26]([C@@H:2]([NH:1][C:29](=[O:30])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[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:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[N:63][C:58]=2[CH:57]=1)[C:52]([CH3:55])([CH3:54])[CH3:53]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 11385960Boc-Asn(Trt)-OHHCID 866990534-Neopentylbenzene-1,2-diamine

Product 1

HCID 178442068HCID 178442068, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of Boc-Asn(Trt)-OH (101 mg, 0.213 mmol) in acetonitrile (2.0 mL) cooled in an ice water bath was added 4-methylmorpholine (0.059 mL, 0.53 mmol) and isobutyl chloroformate (0.027 mL, 0.21 mmol). After stirring for 45 minutes 4-neopentylbenzene-1,2-diamine (Preparation 83, 34 mg, 0.19 mmol) was added and the mixture allowed to warm to room temperature. After stirring for 2.5 hours, the reaction mixture was concentrated in vacuo and acetic acid (1.0 mL, 18 mmol) was added. The reaction was stirred for 18 hours, concentrated in vacuo, redissolved in ethyl acetate, washed with water, aqueous saturated sodium hydrogen carbonate solution, and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to afford the title compound (108 mg, 93%) as an off white solid that was taken directly on to the next step.

Workup

  1. additionwas added
  2. additionwas added
  3. stirringThe reaction was stirred for 18 hours
  4. concentrationconcentrated in vacuo
  5. dissolutionredissolved in ethyl acetate
  6. washwashed with water, aqueous saturated sodium hydrogen carbonate solution, and brine
  7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel column chromatography
  11. washeluting with a 0-100% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-aa7a42c72461402c942dc0e996a39614
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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