N-(tert-butoxycarbonyl)glycine → HCID 57947374, compound

HRID 416346Notes

Reaction equation

HRID 416346 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([NH:12][C:13](=[O:43])[O:14][CH2:15][C@@H:16]([N:29]([CH3:42])[C:30]([NH:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=1[Cl:41])=[O:31])[CH2:17][NH:18]C(OCC1C=CC=CC=1)=O)=[CH:5]2.[Si](I)(C)(C)C.[NH:49]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:50][C:51](O)=[O:52].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC#N.CN(C=O)C.CO>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([NH:12][C:13](=[O:43])[O:14][CH2:15][C@@H:16]([N:29]([CH3:42])[C:30]([NH:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=1[Cl:41])=[O:31])[CH2:17][NH:18][C:51](=[O:52])[CH2:50][NH:49][C:54]([O:56][C:57]([CH3:59])([CH3:58])[CH3:60])=[O:55])=[CH:5]2

Participants

8

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 85247Trimethylsilyl iodideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57947367HCID 57947367, compound

Product 1

HCID 57947374HCID 57947374, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of (S)-3-benzyloxycarbonylamino-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl 6-fluoroisoquinolin-3-ylcarbamate (1.3 g, 2.13 mmol) in CH3CN (20.0 mL) was added TMSI (0.35 mL, 2.56 mmol). The mixture was stirred for 15 min. MeOH (20.0 mL) was added and stirring continued another 15 min. The mixture was concentrated and partitioned between diethyl ether (30 mL) and HCl (2 N, 20 mL). The aqueous layer was separated, adjusted to pH 9, extracted with EtOAc (200 mL×2). The combined organic layers were washed brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give an crude oil, which was dissolved in DMF (6.0 mL). To this DMF solution were added Boc-Gly-OH (0.36 g, 2.03 mmol) and HBTU (0.77 g, 2.03 mmol). The mixture was stirred for 1 h. The crude was filtered and purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-3-(2-tert-butoxycarbonylaminoacetamido)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl 6-fluoroisoquinolin-3-ylcarbamate (0.91 g, 78%). LRMS (M+H+) m/z 635.2.

Workup

  1. stirringstirring
  2. waitcontinued another 15 min
  3. concentrationThe mixture was concentrated
  4. custompartitioned between diethyl ether (30 mL) and HCl (2 N, 20 mL)
  5. customThe aqueous layer was separated
  6. extractionextracted with EtOAc (200 mL×2)
  7. washThe combined organic layers were washed brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give an crude oil, which
  12. stirringThe mixture was stirred for 1 h
  13. filtrationThe crude was filtered
  14. custompurified on RP-HPLC
  15. additiona mixture of acetonitrile and H2O

Sources & evidence

ORD record
ord-91f2382827d7419090490af8fa92b64e
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

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