1,2-Dichloroethane → HCID 58760147, compound

HRID 857769Notes

Reaction equation

HRID 857769 reaction equation
C(OC([N:8]1[CH2:15][CH2:14][C@H:13]([CH3:16])[C@@H:9]1[C:10](O)=[O: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>[CH3:16][C@H:13]1[CH2:14][CH2:15][NH:8][C@H:9]1[C:10]([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:11]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 69655818N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamideHCID 69656213HCID 69656213, compound

Product 1

HCID 58760147HCID 58760147, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

The title compound was prepared from (3S)-1-(tert-butoxycarbonyl)-3-methyl-D-proline (15 mg, 0.07 mmol), N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide (Example 26, Step B, 20 mg, 0.07 mmol, 1.0 equiv), EDC (19 mg, 0.10 mmol, 1.5 equiv) and HOAt (5 mg, 0.03 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)] afforded the compound as a clear oil. 1H NMR (400 MHz, CDCl3): δ 9.10 (s, 1 H), 8.07–8.01 (m, 1 H), 7.56 (app s, 1 H), 7.41 (dd, J=1.6, 8.4 Hz, 1 H), 7.23 (d, J=8.4 Hz, 1 H), 4.65 (br s, 1 H), 4.57–4.55 (m, 1 H), 4.29 (dd, J=6.0, 15.6 Hz, 1 H), 4.05 (dd, J=5.2, 15.2 Hz, 1 H), 3.83–3.77 (m, 1 H), 3.62 (br s, 1 H), 3.45–3.38 (m, 2 H), 2.97 (br s, 1 H), 2.41–1.88 (m, 7 H), 1.01 (d, J=7.2 Hz, 3 H). HRMS (APCI) M+H: calcd for (C19H24N7O2Cl)+ 418.1753, found 418.1741.

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-15686a45ecf74739b728456cb63a080b
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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