1,2-Dichloroethane → 4-methyl-D-leucyl-N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

HRID 857748Notes

Reaction equation

HRID 857748 reaction equation
[NH2:1][C@H:2]([C:7]([OH:9])=O)[CH2:3][CH:4]([CH3:6])[CH3:5].[Cl:10][C:11]1[CH:12]=[CH:13][C:14]([N:26]2[CH:30]=[N:29][N:28]=[N:27]2)=[C:15]([CH:25]=1)[CH2:16][NH:17][C:18](=[O:24])[C@@H:19]1[CH2:23][CH2:22][CH2:21][NH:20]1.[CH2:31](Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH3:31][C:4]([CH3:5])([CH3:6])[CH2:3][C@H:2]([C:7]([N:20]1[CH2:21][CH2:22][CH2:23][C@H:19]1[C:18]([NH:17][CH2:16][C:15]1[CH:25]=[C:11]([Cl:10])[CH:12]=[CH:13][C:14]=1[N:26]1[CH:30]=[N:29][N:28]=[N:27]1)=[O:24])=[O:9])[NH2:1]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 6106L-LeucineHCID 181649HOAtHCID 69655818N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

Product 1

HCID 587601644-methyl-D-leucyl-N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

The title compound was prepared from N-(tert-butoxycarbonyl)-4-methyl]-D-leucine (32 mg, 0.13 mmol), N-[5-chloro-2-(1H-1,2,4-tetraazol-1-yl)benzyl]-L-prolinamide (Example 26, Step B, 50 mg, 0.21 mmol, 1.0 equiv), EDC (38 mg, 0.20 mmol, 1.5 equiv) and HOAt (9 mg, 0.07 mmol, 0.5 equiv) in DMF (1 mL) followed by deprotection in TFA-CH2Cl2 essentially according to the procedure described in Example 27, Step C. Purification by reverse phase chromatography [95:5 water (+0.1% TFA)/CH3CN (+0.1% TFA) to 50:50 water (+0.1% TFA)/CH3CN (+0.1% TFA)] followed by lyophilization of the fractions afforded the title compound as a white powder. 1H NMR (400 MHz, CDCl3): δ 9.18 (s, 1 H), 8.45 (br s, 2 H), 8.00 (t, J=5.2 Hz, 1 H), 7.73 (d, J=2.0 Hz, 1 H), 7.41 (dd, J=2.0, 8.4 Hz, 1 H), 7.19 (d, J=8.4 Hz, 1 H), 4.41–4.34 (m, 2 H), 4.25 (dd, J=4.8, 14.8 Hz, 1 H), 4.00–3.94 (m, 1 H), 3.89–3.85 (m, 1 H), 3.53–3.46 (m, 1 H), 2.25–2.22 (m, 1 H), 2.09–1.85 (m, 5 H), 1.00 (s, 9 H). HRMS (APCI) M+H: calculated for (C20H28N7O2Cl)+ 434.2066, found 434.2065.

Workup

  1. customPurification by reverse phase chromatography [95:5 water (+0.1% TFA)/CH3CN (+0.1% TFA) to 50:50 water (+0.1% TFA)/CH3CN (+0.1% TFA)]

Sources & evidence

ORD record
ord-1c55d26ea7694d1e93b820d18d71e1b4
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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