HCID 69656123, compound → 2-methylleucyl-N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

HRID 857742Notes

Reaction equation

HRID 857742 reaction equation
C(OC([NH:8][C@:9]([CH3:37])([C:14]([N:16]1[CH2:36][CH2:35][CH2:34][C@H:17]1[C:18]([NH:20][CH2:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[N:29]1[CH:33]=[N:32][N:31]=[N:30]1)=[O:19])=[O:15])[CH2:10][CH:11]([CH3:13])[CH3:12])=O)(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH3:37][C@@:9]([C:14]([N:16]1[CH2:36][CH2:35][CH2:34][C@H:17]1[C:18]([NH:20][CH2:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[N:29]1[CH:33]=[N:32][N:31]=[N:30]1)=[O:19])=[O:15])([CH2:10][CH:11]([CH3:13])[CH3:12])[NH2:8]

Participants

3

Reactant 1

HCID 69656123HCID 69656123, compound

Product 1

HCID 696560972-methylleucyl-N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

Each diastereomer of N-(tert-butoxycarbonyl)-2-methylleucyl-N-[5-chloro-2(1H-tetraazol-1-yl)benzyl]-L-prolinamide (A: 86 mg, 0.161 mmol; B: 84 mg, 0.158 mmol) was dissolved in a 2:1 solution of CH2Cl2/TFA (3 mL) and stirred for 1 h. Both reactions were then concentrated to oils. Purification by reverse phase chromatography [95:5 water (+0.1% TFA)/CH3CN (+0.1% TFA) to 5:95 water (+0.1% TFA)/CH3CN (+0.1% TFA)] afforded each diastereomer as a clear oil. Diastereomer A: 1H NMR (300 MHz, CDCl3): δ0 9.32 (s, 1 H), 8.08 (br s, 2 H), 7.78 (t, J=5.1 Hz, 1 H), 7.64 (d, J=2.4Hz, 1 H), 7.44 (dd, J=2.1, 8.7 Hz, 1 H), 7.29 (d, J=8.7 Hz, 1 H), 4.44–4.41 (m, 1 H), 4.23 (m, 2 H), 3.67–3.63 (m, 2 H), 2.28–2.24 (m, 1 H), 2.08–1.85 (m, 5 H), 1.78–1.71 (m, 1 H), 1.68 (s, 3 H), 0.86 (d, J=6.3 Hz, 3 H), 0.78 (d, J=6.6 Hz, 3 H). LCMS (M+H): 434.0. Diastereomer B: 1H NMR (300 MHz, CDCl3): δ 9.17 (s, 1 H), 8.30 (br s, 2 H), 8.08–8.04 (m, 1 H), 7.55 (d, J=2.1 Hz, 1 H), 7.44 (dd, J=2.1, 8.7 Hz, 1 H), 7.30 (d, J=8.7 Hz, 1 H), 4.49–4.45 (m, 1 H), 4.26–4.21 (m, 2 H), 3.77–3.66 (m, 2 H), 2.16–1.80 (m, 6 H), 1.77 (s, 3 H), 1.72–1.66 (m, 1 H), 0.92 (d, J=6.6 Hz, 3 H), 0.79 (d, J=6.3 Hz, 3 H). LCMS (M+H): 434.0.

Workup

  1. concentrationBoth reactions were then concentrated to oils
  2. customPurification by reverse phase chromatography [95:5 water (+0.1% TFA)/CH3CN (+0.1% TFA) to 5:95 water (+0.1% TFA)/CH3CN (+0.1% TFA)]
  3. customafforded each diastereomer as a clear oil

Sources & evidence

ORD record
ord-7ab785c153aa4e509acf7cbf14769204
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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