Citric Acid → HCID 70946002, compound

HRID 133824Notes

Reaction equation

HRID 133824 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-b5f969989d6546de8950b10abddf5165
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Reaction notes

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