1,2-Dichloroethane → 3-methyl-D-valyl-N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

HRID 857746Notes

Reaction equation

HRID 857746 reaction equation
C(OC([NH:8][C@@H:9]([C:14]([OH:16])=O)[C:10]([CH3:13])([CH3:12])[CH3:11])=O)(C)(C)C.[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([N:33]2[CH:37]=[N:36][N:35]=[N:34]2)=[C:22]([CH:32]=1)[CH2:23][NH:24][C:25](=[O:31])[C@@H:26]1[CH2:30][CH2:29][CH2:28][NH:27]1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH3:13][C:10]([CH3:11])([CH3:12])[C@H:9]([C:14]([N:27]1[CH2:28][CH2:29][CH2:30][C@H:26]1[C:25]([NH:24][CH2:23][C:22]1[CH:32]=[C:18]([Cl:17])[CH:19]=[CH:20][C:21]=1[N:33]1[CH:37]=[N:36][N:35]=[N:34]1)=[O:31])=[O:16])[NH2:8]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 7005057(2R)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acidHCID 69655818N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

Product 1

HCID 587601623-methyl-D-valyl-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)-3-methyl-D-valine (53 mg, 0.23 mmol), N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide (Example 26, Step B, 87 mg, 0.23 mmol, 1.0 equiv), EDC (66 mg, 0.34 mmol, 1.5 equiv) and HOAt (16 mg, 0.11 mmol, 0.5 equiv) in DMF (1 mL) followed by deprotection in TFA-CH2Cl2 essentially according to the procedure described in Example 26, 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 (300 MHz, CDCl3): δ 9.22 (s, 1 H), 8.32–8.29 (m, 3 H), 7.85 (d, J=1.8 Hz, 1 H), 7.43 (dd, J=2.1, 8.4 Hz, 1 H), 7.15 (d, J=8.4 Hz, 1 H), 4.45 (app d, J=8.1 Hz, 1 H), 4.35–4.27 (m, 2 H), 3.95–3.79 (m, 2 H), 3.62–3.56 (m, 1 H), 2.31–2.25 (m, 1 H), 2.10–1.87 (m, 3 H), 1.18 (s, 9 H). HRMS (APCI) M+H: calculated for (C19H26N7O2Cl)+ 420.1910, found 420.1915.

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-86c64e5a477f457ba7143c83d7895169
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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