HCID 86602077, compound → HCID 58746705, compound

HRID 724642Notes

Reaction equation

HRID 724642 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([NH:26][C:27](=[O:44])[C@@H:28]([NH:36]C(=O)OC(C)(C)C)[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[S:22](=[O:24])(=[O:23])[NH:21][C:20](=[O:25])[CH:19]=2)=[CH:14][CH:13]=1>FC(F)(F)C(O)=O.C(Cl)Cl>[NH2:36][C@@H:28]([CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:27]([NH:26][C@H:10]([C:2]1[NH:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=1)[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[S:22](=[O:24])(=[O:23])[NH:21][C:20](=[O:25])[CH:19]=2)=[CH:14][CH:13]=1)=[O:44]

Participants

4

Reactant 1

HCID 86602077HCID 86602077, compound

Product 1

HCID 58746705HCID 58746705, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Tert-butyl [(1S)-2-({1-(1H-benzimidazol-2-yl)-2-[4-(1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)phenyl]ethyl}amino)-1-benzyl-2-oxoethyl]carbamate (10 mg, 0.016 mmol) was dissolved in a mixture of trifluoroacetic acid (1 mL) and methylene chloride (1 mL) and stirred for 45 minutes. The solvent was removed in vacuo. The diastereomers alpha to the benzimidazole were resolved through preparative LCMS purification to yield 5.5 mg (95%) of (2S)-2-amino-N-{(1R)-1-(1H-benzimidazol-2-yl)-2-[4-({1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)phenyl]ethyl}-3-phenylpropanamide (Peak A) and 5.5 mg (95%) of (2S)-2-amino-N-{(1S)-1-(1H-benzimidazol-2-yl)-2-[4-(1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)phenyl]ethyl}-3-phenylpropanamide (Peak B). Peak A: 1H NMR (500 MHz, CD3OD): δ 7.84 (d, J=8.4 Hz, 2H), 7.76–7.79 (m, 2H), 7.56–7.59 (m, 2H), 7.43 (d, J=8.4 Hz, 2H), 7.28–7.31 (m, 3H), 7.10–7.13 (m, 2H), 6.93 (s, 1H), 5.59–5.63 (m, 1H), 4.19–4.22 (m, 1H), 3.50–3.55 (m, 1H), 3.32–3.41 (m, 1H), 3.08–3.13 (m, 1H), 2.86–2.91 (m, 1H); LCMS found for C27H25N5O4S (M+H)+: m/z=516.0 Peak B: 1H NMR (500 MHz, CD3OD): δ 7.77–7.82 (m, 4H), 7.62–7.64 (m, 2H), 7.41 (d, J=8.4 Hz, 2H), 6.88–7.01 (m, 6H), 5.61–5.65 (m, 1H), 4.14–4.18 (m, 1H), 3.48–3.53 (m, 2H), 2.97–3.25 (m, 2H); LCMS found for C27H26N5O4S (M+H)+: m/z=516.0

Workup

  1. customThe solvent was removed in vacuo
  2. customThe diastereomers alpha to the benzimidazole were resolved through preparative LCMS purification

Sources & evidence

ORD record
ord-2f607d6ae7de48b682d64908ba3ca8a0
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

Loading…