1,2-Dichloroethane → HCID 69656123, compound

HRID 857741Notes

Reaction equation

HRID 857741 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:17])([CH2:13][CH:14]([CH3:16])[CH3:15])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([N:34]2[CH:38]=[N:37][N:36]=[N:35]2)=[C:23]([CH:33]=1)[CH2:24][NH:25][C:26](=[O:32])[C@@H:27]1[CH2:31][CH2:30][CH2:29][NH:28]1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@:9]([CH3:17])([C:10]([N:28]1[CH2:29][CH2:30][CH2:31][C@H:27]1[C:26]([NH:25][CH2:24][C:23]1[CH:33]=[C:19]([Cl:18])[CH:20]=[CH:21][C:22]=1[N:34]1[CH:38]=[N:37][N:36]=[N:35]1)=[O:32])=[O:12])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 21866228HCID 21866228, compoundHCID 69655818N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

Product 1

HCID 69656123HCID 69656123, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-tert-butyloxycarbonylamino-2,4-dimethylpentanoic acid (120 mg, 0.49 mmol), N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide (150 mg, 0.49 mmol, 1.0 equiv), EDC (141 mg, 0.73 mmol, 1.5 equiv) and HOAt (33 mg, 0.24 mmol, 0.5 equiv) in DMF (1 ml) was brought to pH 8 by dropwise addition of Hünig's Base and stirred at room temperature for 18 h. The solvent was removed in vacuo, and the resulting oil was purified by silica gel chromatography (50% EtOAc-hexanes to 70% EtOAc-hexanes to EtOAc) to afford the two separate diastereomers as white solids. Diastereomer A (less polar): 1H NMR (300 MHz, CDCl3): δ 9.32 (s, 1 H), 8.10 (t, J=5.4 Hz, 1 H), 7.72 (d, J=2.1 Hz, 1 H), 7.40 (dd, J=2.1, 8.1 Hz, 1 H), 7.27 (d, J=8.1 Hz, 1 H), 5.03 (s, 1 H), 4.55–4.50 (m, 1 H), 4.23 (dd, J=6.3, 15.3 Hz, 1 H), 4.01 (dd, J=5.1, 15.3 Hz, 1 H), 3.84–3.79 (m, 1 H), 3.55–3.52 (m, 1 H), 2.22–2.12 (m, 1 H), 1.95–1.68 (m, 5 H), 1.59 (s, 3 H), 1.51–1.45 (m, 1 H), 1.34 (s, 9 H), 0.98 (d, J=6.6 Hz, 3 H), 0.85 (d, J=6.3 Hz, 3 H). Diastereomer B (more polar): 1H NMR (300 MHz, CDCl3): δ 9.29 (s, 1 H), 8.11–8.08 (m, 1 H), 7.70 (d, J=2.1 Hz, 1 H), 7.39 (dd, J=2.1, 8.4 Hz, 1 H), 7.26 (d, J=8.4 Hz, 1 H), 5.21 (s, 1 H), 4.59–4.54 (m, 1 H), 4.25 (dd, J=6.3, 15.3 Hz, 1 H), 4.00 (dd, J=4.8, 15.3 Hz, 1 H), 3.85–3.79 (m, 1 H), 3.53–3.49 (m, 1 H), 2.24–2.22 (m, 1 H), 1.97–1.83 (m, 5 H), 1.66–1.60 (m, 1 H), 1.39 (s, 3 H), 1.36 (s, 9 H), 0.97 (d, J=6.3 Hz, 3 H), 0.91 (d, J=6.6Hz, 3 H). Diastereomeric mixture: LCMS (M+H): 534.0.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe resulting oil was purified by silica gel chromatography (50% EtOAc-hexanes to 70% EtOAc-hexanes to EtOAc)
  3. customto afford the two
  4. customseparate diastereomers as white solids

Sources & evidence

ORD record
ord-3df07aec3ea34a02a4311f82cf7c5fbb
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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