4-Methylmorpholine → HCID 67407303, compound

HRID 1949643Notes

Reaction equation

HRID 1949643 reaction equation
[NH:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:2]([C:5]([OH:7])=O)[CH2:3][CH3:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[F:46][C:47]1[CH:55]=[C:54]2[C:50]([C:51]([CH:56]3[CH2:60][N:59]([S:61]([CH3:64])(=[O:63])=[O:62])[CH:58]4[CH2:65][CH2:66][NH:67][CH:57]34)=[CH:52][NH:53]2)=[CH:49][CH:48]=1>CN1C(=O)CCC1.C(OCC)C.CCOC(C)=O>[C:11]([O:10][C:8](=[O:9])[NH:1][CH:2]([C:5]([N:67]1[CH2:66][CH2:65][CH:58]2[N:59]([S:61]([CH3:64])(=[O:63])=[O:62])[CH2:60][CH:56]([C:51]3[C:50]4[C:54](=[CH:55][C:47]([F:46])=[CH:48][CH:49]=4)[NH:53][CH:52]=3)[CH:57]12)=[O:7])[CH2:3][CH3:4])([CH3:14])([CH3:13])[CH3:12]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 2755934(S)-2-((tert)-Butoxycarbonyl)amino)butanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67410675HCID 67410675, compound

Product 1

HCID 67407303HCID 67407303, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution containing Boc-L-Abu-OH (170 mg, 0.83 mmol) in anhydrous NMP (2 mL) was cooled to 0° C. HATU (316 mg, 0.83 mmol) and NMM (115 mg, 1.08 mmol) were added followed by the addition of crude 63 (242 mg, 0.75 mmol) in anhydrous NMP (4 mL). The reaction mixture was slowly warmed to ambient temperature. After 16 h, the reaction mixture was diluted with diethyl ether and EtOAc (10:1) and washed successively with aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by RP-HPLC (2″ Dynamax C18, 40-100% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min) to afford 270 mg (71%) of 64. Mass spectrum, m/z [509.2] (M+H)+.

Workup

  1. temperatureThe reaction mixture was slowly warmed to ambient temperature
  2. washwashed successively with aqueous NaHCO3 and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by RP-HPLC (2″ Dynamax C18, 40-100% ACN/water containing 0.1% HOAc over 30 min

Sources & evidence

ORD record
ord-38a7582a04de4c62b8131c17bdb229d9
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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