3-(S)-(2-(S)-Benzyloxycarbonylamino-4,4-dimethyl-pentanoylamino)-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid tert-butyl ester → 3-(s)-(2-(s)-Benzyloxycarbonylamino-4,4-dimethyl-pentanoylamino)-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid

HRID 132144Notes

Reaction equation

HRID 132144 reaction equation
C([O:5][C:6](=[O:40])[CH2:7][C@H:8]([NH:20][C:21](=[O:39])[C@@H:22]([NH:28][C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30])[CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:9][N:10]1[C:18]2[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=2)[CH2:12][CH2:11]1)(C)(C)C>C(O)(C(F)(F)F)=O.ClCCl.O>[CH2:32]([O:31][C:29]([NH:28][C@@H:22]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:21]([NH:20][C@H:8]([CH2:9][N:10]1[C:18]2[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=2)[CH2:12][CH2:11]1)[CH2:7][C:6]([OH:40])=[O:5])=[O:39])=[O:30])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

5

Reactant 1

HCID 691960933-(S)-(2-(S)-Benzyloxycarbonylamino-4,4-dimethyl-pentanoylamino)-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid tert-butyl ester

Product 1

HCID 691942473-(s)-(2-(s)-Benzyloxycarbonylamino-4,4-dimethyl-pentanoylamino)-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent2×

Procedure

The title compound of example 158 (46 mg, 83 μmol) was dissolved in a mixture of TFA, dichloromethane and water in a ratio of 45:45:10 (1 mL) and stirred overnight. The solvent was removed and the reaction was lyophilized to afford 58.1 mg (114% of theory) of material that likely had some water or multiple TFA salts included; 1H NMR (MeOD, 400 MHz) δ 0.91 (s, 9H), 1.49 (dd, 1H, J1=9.3, J2=14.4), 1.67 (dd, 1H, J1=3.1, J2=14.5), 2.63 (d, 1H, J=6.5), 2.98 (dd, 1H, J1=J2=8.1), 3.17 (dd, 1H, J1=5.5, J2=13.6), 3.26-3.34 (m, 1H), 3.47 (dd, 1H, J1=8.6, J2=17.3), 3.58 (dd, 1H, J1=8.4, J2=16.6), 4.13 (dd, 1H, J1=3.0, J2=9.3), 4.46-4.55 (m, 1H), 4.98-5.11 (m, 2H), 6.68 (dd, 1H, J1=4.1, J2=8.6), 6.77-6.84 (m, 1H), 6.86-6.91 (m, 1H), 7.24-7:33 (m, 5H); HPLC-MS calcd. for C27H34FN3O5 (M+H+) 500.2, found 500.5.

Workup

  1. customThe solvent was removed
  2. customto afford 58.1 mg (114% of theory) of material

Sources & evidence

ORD record
ord-e84abcdb16b8423f86f50c192ef7956e
Source dataset
uspto-grants-2008_06
Patent number
US07384970B2

Reaction notes

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