Trifluoroacetic acid → HCID 66740735, compound

HRID 1627269Notes

Reaction equation

HRID 1627269 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:35])[C:8]=1[CH2:9][S:10][C:11]1[N:12]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:13]([C:16]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([O:26][CH3:27])[CH:20]=2)([CH3:18])[CH3:17])=[CH:14][N:15]=1)[NH2:5].C([O:40][C:41](=[O:55])[CH2:42][C@H:43]([NH:47]C(OC(C)(C)C)=O)[C:44](O)=[O:45])(C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:47][C@H:43]([C:44]([NH:5][C:4]1[CH:6]=[C:7]([F:35])[C:8]([CH2:9][S:10][C:11]2[N:12]([C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[C:13]([C:16]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([O:26][CH3:27])[CH:20]=3)([CH3:17])[CH3:18])=[CH:14][N:15]=2)=[C:2]([Cl:1])[CH:3]=1)=[O:45])[CH2:42][C:41]([OH:55])=[O:40]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 70106364-(1,1-Dimethylethyl) hydrogen N-[(1,1-dimethylethoxy)carbonyl]-L-aspartateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66739983HCID 66739983, compound

Product 1

HCID 66740735HCID 66740735, compoundYield 18.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluoroaniline (50 mg, 93.6 μmol) and (S)-4-t-butoxy-2-(t-butoxycarbonylamino)-4-oxobutanoic acid (2.4 equiv, 66 mg, 0.244 mmol) in DCM (3 mL) was added HATU (2.2 equiv, 80 mg, 0.204 mmol) followed by DIPEA (3.0 equiv, 49 mL, 0.281 mmol). The mixture was stirred at room temperature overnight. Purification by column chromatography provided the protected product. Deprotection was performed by stirring with TFA (1 mL) and DCM (1 mL) for 1 h. Purification by HPLC using NH4CO3 as a modifier afforded the title compound as a white solid (11 mg, 18%). 1H NMR (400 MHz, MeOD) δ 7.43 (s, 1H), 7.37 (d, J=11.6 Hz, 1H), 7.25 (s, 1H), 7.18 (d, J=8.4 Hz, 1H), 6.80 (m, 2H), 6.56-6.49 (m, 2H), 6.38-6.30 (m, 1H), 6.22 (m, 1H), 4.19 (t, J=7.6, 1H), 4.00 (dd, J=13.5, 7.4 Hz, 2H), 3.71 (s, 3H), 2.89-2.78 (m, 1H), 2.67 (dd, J=17.0, 8.1 Hz, 1H), 1.54 (s, 3H), 1.53 (s, 3H); MS (EI) m/z 649 (MH+).

Workup

  1. customPurification by column chromatography
  2. customprovided the protected product
  3. customPurification by HPLC

Sources & evidence

ORD record
ord-1bed07e2bb014109962550ed486ec025
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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