Methyl N-(triethylammoniosulfonyl)carbamate → (S)-tert-butyl 4-(1-cyano-2-(4'-(ethylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216905Notes

Reaction equation

HRID 216905 reaction equation
NC(=O)[C@@H](NC(C1(NC(=O)OC(C)(C)C)CCOCC1)=O)CC1C=CC(C2C=CC(C(F)(F)F)=CC=2)=CC=1.[NH2:39][C:40](=O)[C@@H:41]([NH:60][C:61]([C:63]1([NH:69][C:70](=[O:76])[O:71][C:72]([CH3:75])([CH3:74])[CH3:73])[CH2:68][CH2:67][O:66][CH2:65][CH2:64]1)=[O:62])[CH2:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]2[CH:54]=[CH:53][C:52]([S:55]([CH2:58][CH3:59])(=[O:57])=[O:56])=[CH:51][CH:50]=2)=[CH:45][CH:44]=1.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>ClCCl>[C:40]([C@@H:41]([NH:60][C:61]([C:63]1([NH:69][C:70](=[O:76])[O:71][C:72]([CH3:75])([CH3:74])[CH3:73])[CH2:68][CH2:67][O:66][CH2:65][CH2:64]1)=[O:62])[CH2:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]2[CH:54]=[CH:53][C:52]([S:55]([CH2:58][CH3:59])(=[O:57])=[O:56])=[CH:51][CH:50]=2)=[CH:45][CH:44]=1)#[N:39]

Participants

5

Reactant 3

HCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 59568598(S)-tert-butyl 4-(1-amino-1-oxo-3-(4'-(trifluoromethyl)biphenyl-4-yl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateHCID 59568601(S)-tert-butyl 4-(1-amino-3-(4'-(ethylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 59568561(S)-tert-butyl 4-(1-cyano-2-(4'-(ethylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The mixture of (S)-tert-butyl 4-(1-amino-1-oxo-3-(4′-(trifluoromethyl)biphenyl-4-yl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate and (S)-tert-butyl 4-(1-amino-3-(4′-(ethylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 1, step (iv), 1.7 g) in dichloromethane (15 mL) was treated with Burgess' reagent (1.19 g) and the mixture was stirred at room temperature for 72 h. The reaction was evaporated onto silica and purified on a silica column eluting with 20% ethyl acetate in isohexane, then 50% ethyl acetate in isohexane and finally 100% ethyl acetate to afford after evaporation of the relevant fractions (S)-tert-butyl 4-(1-cyano-2-(4′-(trifluoromethyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (650 mg) and (S)-tert-butyl 4-(1-cyano-2-(4′-(ethylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (920 mg).

Workup

  1. customThe reaction was evaporated onto silica
  2. custompurified on a silica column
  3. washeluting with 20% ethyl acetate in isohexane
  4. custom50% ethyl acetate in isohexane and finally 100% ethyl acetate to afford
  5. customafter evaporation of the relevant fractions (S)-tert-butyl 4-(1-cyano-2-(4′-(trifluoromethyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (650 mg) and (S)-tert-butyl 4-(1-cyano-2-(4′-(ethylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (920 mg)

Sources & evidence

ORD record
ord-52e35b59fc9f4f55a3495e97bf1c4c39
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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