1,2-Dichloroethane → HCID 58760149, compound

HRID 857745Notes

Reaction equation

HRID 857745 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][CH: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.CCN(C(C)C)C(C)C>CN(C=O)C>[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][CH:35]=[N:34]1)=[O:31])=[O:16])[NH2:8]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 7005057(2R)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acidHCID 69656007HCID 69656007, compound

Product 1

HCID 58760149HCID 58760149, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of N-(tert-butoxycarbonyl)-3-methyl-D-valine (53 mg, 0.23 mmol), N-[5-chloro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide (87 mg, 0.23 mmol, 1.0 equiv), EDC (66 mg, 0.34 mmol, 1.5 equiv), HOAt (16 mg, 0.11 mmol, 0.5 equiv) in DMF (1 mL) was brought to pH 6 by addition of Hünig's base and stirred at room temperature for 18 h. The solvent was removed in vacuo, and the resulting residue was dissolved in 2:1 CH2Cl2/TFA (3 mL) and stirred for 1 h. Solvent was again removed in vacuo, and 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 title compound as a clear oil. 1H NMR (400 MHz, CDCl3): δ 8.93 (s, 1 H), 8.29 (s, 1 H), 8.00 (br s, 1 H), 7.55 (d, J=2.0 Hz, 1 H), 7.39 (dd, J=2.0, 8.4 Hz, 1 H), 7.25 (d, J=8.4 Hz, 1 H), 7.01 (br s, 2 H), 4.47–4.45 (m, 1 H), 4.35–4.30 (m, 2 H), 4.15 (dd, J=5.2, 15.2 Hz, 1 H), 3.80–3.71 (m, 1 H), 3.58–3.52 (m, 1 H), 2.15–2.12 (m, 2 H), 2.01–1.98 (m, 2 H), 1.10 (s, 9 H). HRMS (APCI) M+H: calculated for (C20H27N6O2Cl)+ 419.1957, found 419.1935.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe resulting residue was dissolved in 2:1 CH2Cl2/TFA (3 mL)
  3. stirringstirred for 1 h
  4. customSolvent was again removed in vacuo, and 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)]

Sources & evidence

ORD record
ord-fc4fdbfd9b814cde9325670c31871e40
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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