4-Methylmorpholine → HCID 67149061, compound

HRID 1054016Notes

Reaction equation

HRID 1054016 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([C:16]([OH:18])=O)[CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:7])([CH3:4])[CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[F:50][C:51]1[CH:59]=[C:58]2[C:54]([C:55]([CH2:70][CH:71]3[CH2:75][CH2:74][CH2:73][NH:72]3)=[CH:56][N:57]2[CH2:60][CH2:61][O:62][CH2:63][CH2:64][O:65][CH2:66][CH2:67][O:68][CH3:69])=[CH:53][CH:52]=1>CN1C(=O)CCC1.C(Cl)Cl.C(OCC)(=O)C>[C:2]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]1)[C:16]([N:72]1[CH2:73][CH2:74][CH2:75][CH:71]1[CH2:70][C:55]1[C:54]2[C:58](=[CH:59][C:51]([F:50])=[CH:52][CH:53]=2)[N:57]([CH2:60][CH2:61][O:62][CH2:63][CH2:64][O:65][CH2:66][CH2:67][O:68][CH3:69])[CH:56]=1)=[O:18])([CH3:1])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67148621HCID 67148621, compound

Product 1

HCID 67149061HCID 67149061, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of Boc-L-cyclohexylglycine (172 mg, 0.67 mmol) in NMP (2 mL) was added HATU (255 mg, 0.67 mmol) followed by NMM (0.1 mL, 0.95 mmol). After 5 min, 81 (190 mg, 0.55 mmol) in DCM (1 mL) was added and the reaction mixture was stirred at room temperature overnight. Ethyl acetate (20 mL) was added to the reaction mixture and the organic solution was washed with water, 1 N HCl (5 mL), aqueous NaHCO3 (10 mL), and brine, dried over Na2SO4. Solvent was removed under reduced pressure and the product was purified by flash silica gel chromatography to afford 280 mg (85%) of 82 as a wax. [TLC (60% EtOAc/hexane): Rf(82)=0.18)]. 1H NMR (CDCl3, 300 MHz) δ 7.83 (m, 1H), 7.32 (m, 1H), 7.20 (m, 1H), 7.09 (m, 1H), 6.98 (s, 1H), 5.32 (m, 1H), 4.0-4.6 (5H), 3.79 (t, J=5.7 Hz, 2H), 3.40-3.70 (9H), 3.37 (s, 3H), 2.65 (m, 1H), 1.6-2.0 (10H), 1.46 (s, 9H), 1.0-1.4 (6H) ppm.

Workup

  1. washthe organic solution was washed with water, 1 N HCl (5 mL), aqueous NaHCO3 (10 mL), and brine
  2. dry with materialdried over Na2SO4
  3. customSolvent was removed under reduced pressure
  4. customthe product was purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-08efc13dc90343c8855825312953584e
Source dataset
uspto-grants-2016_07
Patent number
US09394249B2

Reaction notes

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