1,8-Diazabicyclo(5.4.0)undec-7-ene → tert-butyl N-[(3S,3aR,6R,6aR)-3-[[6-chloro-5-(4-phenylphenyl)-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]amino]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]carbamate

HRID 929231Notes

Reaction equation

HRID 929231 reaction equation
C1CCN2C(=NCCC2)CC1.[Cl:12][C:13]1[CH:14]=[C:15]2[N:33]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[C:32](S(C)(=O)=O)=[N:31][C:16]2=[N:17][C:18]=1[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:21][CH:20]=1.[NH2:46][C@H:47]1[CH2:51][O:50][C@@H:49]2[C@H:52]([NH:55][C:56](=[O:62])[O:57][C:58]([CH3:61])([CH3:60])[CH3:59])[CH2:53][O:54][C@H:48]12>CN(C=O)C.C(OCC)(=O)C>[Cl:12][C:13]1[CH:14]=[C:15]2[N:33]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[C:32]([NH:46][C@H:47]3[CH2:51][O:50][C@@H:49]4[C@H:52]([NH:55][C:56](=[O:62])[O:57][C:58]([CH3:60])([CH3:59])[CH3:61])[CH2:53][O:54][C@H:48]34)=[N:31][C:16]2=[N:17][C:18]=1[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 682826082-[[6-Chloro-2-methylsulfonyl-5-(4-phenylphenyl)imidazo[4,5-b]pyridin-1-yl]methoxy]ethyl-trimethyl-silaneHCID 90042669tert-Butyl ((3R,3aR,6S,6aR)-6-aminohexahydrofuro[3,2-b]furan-3-yl)carbamate

Product 1

HCID 131735103tert-butyl N-[(3S,3aR,6R,6aR)-3-[[6-chloro-5-(4-phenylphenyl)-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]amino]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]carbamate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DBU (18.3 uL, 0.122 mmol) was added to a mixture of 2-[[6-chloro-2-methylsulfonyl-5-(4-phenylphenyl)imidazo[4,5-b]pyridin-1-yl]methoxy]ethyl-trimethyl-silane (50 mg, 0.097 mmol) and tert-butyl N-[(3S,3aR,6R,6aR)-3-amino-2,3,3a,5,6,6a-hexahydrofuro-[3,2-b]furan-6-yl]carbamate (72.6 mg, 0.297 mmol) in DMF (0.39 mL). After 18 hours, the mixture was diluted with ethyl acetate (20 mL) and washed with water (5×20 mL). The organic layer was separate, washed with brine (1×10 mL), dried with MgSO4, filtered and the solvent was removed under vacuum. The crude reaction mixture was then purified on preparative silica gel plates (1×1000 u—developed with 30% EtOAc/hexanes and eluted with EtOAc) to give the title compound. LC-MS: calculated for C35H44ClN5O5Si 677.28 observed m/e minor isomer 678.31 (M+H)+ (Rt 1.34/2 min) and major isomer 608.23 (M+H)+ (Rt 1.04/2 min)

Workup

  1. washwashed with water (5×20 mL)
  2. customThe organic layer was separate
  3. washwashed with brine (1×10 mL)
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. customthe solvent was removed under vacuum
  7. customThe crude reaction mixture
  8. customwas then purified on preparative silica gel plates (1×1000 u—developed with 30% EtOAc/hexanes and eluted with EtOAc)

Sources & evidence

ORD record
ord-4c70b8d872994d4f992b16a94e37e142
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

Loading…