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

HRID 216915Notes

Reaction equation

HRID 216915 reaction equation
NC(=O)[C@@H](NC(C1(NC(=O)OC(C)(C)C)CCOCC1)=O)CC1C=CC(C2C=CC(F)=CC=2)=CC=1.[NH2:36][C:37](=O)[C@@H:38]([NH:58][C:59]([C:61]1([NH:67][C:68](=[O:74])[O:69][C:70]([CH3:73])([CH3:72])[CH3:71])[CH2:66][CH2:65][O:64][CH2:63][CH2:62]1)=[O:60])[CH2:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]2[CH:51]=[CH:50][C:49]([S:52]([CH:55]([CH3:57])[CH3:56])(=[O:54])=[O:53])=[CH:48][CH:47]=2)=[CH:42][CH:41]=1.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>ClCCl>[C:37]([C@@H:38]([NH:58][C:59]([C:61]1([NH:67][C:68](=[O:74])[O:69][C:70]([CH3:71])([CH3:73])[CH3:72])[CH2:66][CH2:65][O:64][CH2:63][CH2:62]1)=[O:60])[CH2:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]2[CH:51]=[CH:50][C:49]([S:52]([CH:55]([CH3:57])[CH3:56])(=[O:54])=[O:53])=[CH:48][CH:47]=2)=[CH:42][CH:41]=1)#[N:36]

Participants

5

Reactant 3

HCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 59568578(S)-tert-butyl 4-(1-amino-3-(4'-(isopropylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateHCID 59568602(S)-tert-butyl 4-(1-amino-3-(4'-fluorobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 59568606(S)-tert-butyl 4-(1-cyano-2-(4'-(isopropylsulfonyl)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-3-(4′-fluorobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate and (S)-tert-butyl 4-(1-amino-3-(4′-(isopropylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 4, step (i), 620 mg) in dichloromethane (15 mL) was treated with Burgess' reagent (462 mg) and the mixture was stirred at room temperature for 2 days. The reaction was absorbed onto silica and was purified by chromatography on silica eluting with 25% ethyl acetate in isohexane and then 50% ethyl acetate in isohexane to afford after evaporation of the relevant fractions (S)-tert-butyl 4-(1-cyano-2-(4′-fluorobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (218 mg) and (S)-tert-butyl 4-(1-cyano-2-(4′-(isopropylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (300 mg).

Workup

  1. customThe reaction was absorbed onto silica
  2. customwas purified by chromatography on silica eluting with 25% ethyl acetate in isohexane
  3. custom50% ethyl acetate in isohexane to afford
  4. customafter evaporation of the relevant fractions (S)-tert-butyl 4-(1-cyano-2-(4′-fluorobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (218 mg) and (S)-tert-butyl 4-(1-cyano-2-(4′-(isopropylsulfonyl)biphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (300 mg)

Sources & evidence

ORD record
ord-cfcf682180584657b0a7b834e5fba82a
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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