Trifluoroacetic acid → HCID 10233793, compound

HRID 1582729Notes

Reaction equation

HRID 1582729 reaction equation
OC(C(F)(F)F)=O.[CH3:8][S:9][CH:10]([CH:23]1[CH2:27][CH2:26][CH2:25][NH:24]1)[CH2:11][C:12]([NH:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:13].[CH3:28][N:29]([CH3:57])[C@H:30]([C:34]([NH:36][C@H:37]([C:41]([N:43]([C@@H:45]([C@@H:53]([CH3:56])[CH2:54][CH3:55])[C@H:46]([O:51][CH3:52])[CH2:47][C:48](O)=[O:49])[CH3:44])=[O:42])[CH:38]([CH3:40])[CH3:39])=[O:35])[CH:31]([CH3:33])[CH3:32].C(O)(C(F)(F)F)=O.P(C#N)(=O)(OCC)OCC.C(N(CC)CC)C>CN(C=O)C.C(Cl)Cl>[CH:53]([CH:45]([N:43]([CH3:44])[C:41]([CH:37]([NH:36][C:34](=[O:35])[CH:30]([N:29]([CH3:57])[CH3:28])[CH:31]([CH3:32])[CH3:33])[CH:38]([CH3:39])[CH3:40])=[O:42])[CH:46]([O:51][CH3:52])[CH2:47][C:48]([N:24]1[CH2:25][CH2:26][CH2:27][CH:23]1[CH:10]([S:9][CH3:8])[CH2:11][C:12](=[O:13])[NH:14][CH2:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:49])([CH2:54][CH3:55])[CH3:56]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 10812513HCID 10812513, compoundHCID 86587441HCID 86587441, compound

Product 1

HCID 10233793HCID 10233793, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

After the crude 3-methylsulfanyl-N-phenethyl-3-pyrrolidin-2-yl-propionamide TFA salt obtained above was dissolved in DMF(2 ml), the solution was added at 0° C. to (3R*,4S*,5S*)-4-[N,N-dimethyl-L-valyl-(N-methyl-L-valinamido)]-3-methoxy-5-methylheptanoic acid which was prepared from (3R*,4S*,5S*)-4-[N,N-dimethyl-L-valyl-(N-methyl-L-valinamido)]-3-methoxy-5-methylheptanoic acid t-Bu ester (34 mg, 0.0700 mmol) by treating with TFA in CH2Cl2 according to the literature method (Chem. Pharm. Bull., 43(10), 1706-1718, 1995). To the solution were added diethyl phosphorocyanidate (95%: 12 μl, 0.0751 mmol) and triethylamine (49 μl, 0.352 mmol) at 0° C. After being stirred at 0° C. for 1 hr, the mixture was allowed to warm to room temperature and stirred for 20 hr. The mixture was quenched with saturated aqueous NaHCO3, extracted with AcOET, washed with saturated aqueous NaCl, dried (MgSO4), and concentrated in vacuo to give the crude oil (90 mg), which was purified by preparative HPLC (column: ODS-80Ts, eluent: 39/31 H2O:CH3CN/0.05% TFA). The appropriate fractions were lyophilized to obtain the title compound as a white amorphous powder (30 mg, 47%).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 20 hr
  3. customThe mixture was quenched with saturated aqueous NaHCO3
  4. extractionextracted with AcOET
  5. washwashed with saturated aqueous NaCl
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto give the crude oil (90 mg), which
  9. customwas purified by preparative HPLC (column: ODS-80Ts, eluent: 39/31 H2O:CH3CN/0.05% TFA)

Sources & evidence

ORD record
ord-c2430d4ddb0d439fb901ff18896bf33d
Source dataset
uspto-grants-2004_05
Patent number
US06737409B2

Reaction notes

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