Trifluoroacetic acid → HCID 9892386, compound

HRID 1391979Notes

Reaction equation

HRID 1391979 reaction equation
C(OC(=O)[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([C@@H:13]([CH2:19][N:20](C(OCC2C=CC=CC=2)=O)[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][C:23]=2[CH3:29])[C@@H:14]([OH:18])[C:15]#[C:16][CH3:17])[C:9]1=[O:40])(C)(C)C.C(O)(C(F)(F)F)=O.C(N(CC)C(C)C)(C)C.[F:58][C:59]([F:70])([F:69])[C:60]1[CH:61]=[C:62]([CH:66]=[CH:67][CH:68]=1)[C:63]([OH:65])=O.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:29][C:23]1[CH:24]=[C:25]([CH3:28])[CH:26]=[CH:27][C:22]=1[CH2:21][NH:20][CH2:19][C@H:13]([N:10]1[CH2:11][CH2:12][C@H:8]([NH:7][C:63](=[O:65])[C:62]2[CH:66]=[CH:67][CH:68]=[C:60]([C:59]([F:58])([F:70])[F:69])[CH:61]=2)[C:9]1=[O:40])[C@@H:14]([OH:18])[CH2:15][CH2:16][CH3:17]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 99633-(Trifluoromethyl)benzoic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 69292175HCID 69292175, compound

Product 1

HCID 9892386HCID 9892386, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of {(3S)-1-[(1S,2S)-(1-{[benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pent-3-ynyl)]-2-oxo-pyrrolidin-3-yl}-carbamic acid tert-butyl ester (1.16 g, 1.74 mmol) was dissolved in CH2Cl2 (16 mL) and treated with TFA (8 mL). The solution was stirred for 3 h and then concentrated in vacuo. The residue was dissolved in CH2Cl2 and concentrated in vacuo; this procedure was repeated. A portion (0.22 mmol) of the product amine was dissolved in CH2Cl2 (4 mL). The resultant solution was charged sequentially with N, N-diisopropylethylamine (0.16 mL, 0.88 mmol), 4-dimethylaminopyridine (24 mg, 0.22 mmol), meta-trifluoromethylbenzoic acid (41 mg, 0.22 mmol), and BOP (96 mg, 0.22 mmol). The reaction was stirred for 12 h and partitioned between EtOAc and sat. NH4Cl. The organic phase was washed with sat. NaHCO3 and brine, and then dried (Na2SO4), filtered, and concentrated in vacuo. The residue was dissolved in MeOH (6 mL). The resultant solution was charged with 5% Pd/C, Degussa style (50 mg), stirred under H2 (1 atm) for 12 h at RT, filtered, and concentrated in vacuo. The residue was purified by reverse-phase HPLC to afford the title compound as a white powder after lyopholization. MS found: (M+H)+=506.6.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2
  3. concentrationconcentrated in vacuo
  4. stirringThe reaction was stirred for 12 h
  5. custompartitioned between EtOAc and sat. NH4Cl
  6. washThe organic phase was washed with sat. NaHCO3 and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in MeOH (6 mL)
  11. additionThe resultant solution was charged with 5% Pd/C, Degussa style (50 mg)
  12. stirringstirred under H2 (1 atm) for 12 h at RT
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-efcc9184f9aa42359c5a33f1135fc838
Source dataset
uspto-grants-2008_03
Patent number
US07338975B2

Reaction notes

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