1,2-Dichloroethane → N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-1-[1-(tert-butoxycarbonyl)-(2R)-piperidin-2-ylcarbonyl]-L-prolinamide

HRID 857763Notes

Reaction equation

HRID 857763 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[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.CC#N.O>[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][N:27]1[C:14]([C@H:9]1[CH2:10][CH2:11][CH2:12][CH2:13][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:16]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 688618(2R)-1-[(tert-butoxy)carbonyl]piperidine-2-carboxylic acidHCID 69655818N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

Product 1

HCID 69655970N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-1-[1-(tert-butoxycarbonyl)-(2R)-piperidin-2-ylcarbonyl]-L-prolinamide

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×

Procedure

The title compound was prepared from (2R)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (52 mg, 0.23 mmol), N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide (Example 26, Step B, 70 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 (500 μl) essentially according to the procedure described in Example 26, Step C. Reverse phase HPLC [95:5 water (+0.1% TFA)/CH3CN (+0.1% TFA) to 5:95 water (+0.1% TFA)/CH3CN (+0.1% TFA)] afforded the title compound as a clear oil. 1H NMR (400 MHz, CDCl3): δ 9.16 (s, 1 H), 7.90 (br s, 1 H), 7.59 (s, 1 H), 7.41 (d, J=8.4 Hz, 1 H), 7.24 (d, J =8.4 Hz, 1 H), 4.56 (br s, 1 H), 4.38 (br s, 1 H), 4.18–4.15 (m, 2 H), 3.80 (br s, 1 H), 3.58–3.52 (m, 3 H), 2.15–2.11 (m, 2 H), 2.05–1.98 (m, 2 H), 1.95–1.84 (m, 2 H), 1.70–1.68 (m, 2 H), 1.55 (br s, 2 H), 1.33 (s, 9 H). LCMS (M+H): 518.3.

Sources & evidence

ORD record
ord-db805e102f66481dbd8a3b9c48ec7cd3
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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