Citric Acid → HCID 70946002, compound

HRID 1865729Notes

Reaction equation

HRID 1865729 reaction equation
FC(F)(F)[C:3]([OH:5])=[O:4].[NH2:8][C@@H:9]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:10]([N:12]([C@@H:14]([CH:19]([CH3:21])[CH3:20])/[CH:15]=[CH:16]/[C:17]#[N:18])[CH3:13])=[O:11].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.C(O[C:74]([N:76](C)[C@@H:77]([C:81]([CH3:89])([C:83]1[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=1)[CH3:82])[C:78](O)=[O:79])=O)(C)(C)C.C(O)(=O)[CH2:92][C:93]([CH2:98]C(O)=O)([C:95](O)=O)O>CCCCCC.CCOCC.ClCCl>[C:17](/[CH:16]=[CH:15]/[C@@H:14]([N:12]([CH3:13])[C:10]([C@@H:9]([NH:8][C:78]([C@@H:77]([N:76]([CH3:74])[C:3](=[O:4])[O:5][C:93]([CH3:98])([CH3:95])[CH3:92])[C:81]([CH3:82])([C:83]1[CH:84]=[CH:85][CH:86]=[CH:87][CH:88]=1)[CH3:89])=[O:79])[C:22]([CH3:23])([CH3:25])[CH3:24])=[O:11])[CH:19]([CH3:20])[CH3:21])#[N:18]

Participants

9

Reactant 6

HCID 311Citric AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10425339HCID 10425339, compoundHCID 86596609HCID 86596609, compound

Product 1

HCID 70946002HCID 70946002, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21584099Diethylether hexaneSolvent

Procedure

To (2S)-2-amino-N-[(1S,2E)-3-cyano-1-isopropyl-2-propenyl]-N,3,3-trimethylbutanamide trifluoroacetic acid (179 mg, from Reference Example 16), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 297 mg) and 1-Hydroxy-7-azabenzotriazole (HOAt, 6.8 mg) is added diisopropylethylamine (252 uL) followed by dichloromethane (9 mL) and (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-methyl-3-phenylbutanoic acid (162 mg). After 18 h 5% aqueous citric acid is added. The aqueous phase is washed with dichloromethane three times. The combined organic extracts are dried over anhydrous magnesium sulfate and concentrated in vacuo to give a yellow oil. Chromatography (silica gel, hexane/ether) gave the title compound as a yellow foam (176 mg). MS (ES): m/z 541.1 (M+H)

Workup

  1. washThe aqueous phase is washed with dichloromethane three times
  2. dry with materialThe combined organic extracts are dried over anhydrous magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customto give a yellow oil

Sources & evidence

ORD record
ord-22cb354117f64b2d911b8af0a2a2bd5d
Source dataset
uspto-grants-2009_12
Patent number
US07626023B2

Reaction notes

Loading…