1,1'-Carbonyldiimidazole → HCID 178461238, compound

HRID 81243Notes

Reaction equation

HRID 81243 reaction equation
[Cl:1][C:2]1[C:3]2[N:21]=[C:20]([N:22]3[CH2:27][CH2:26][O:25][C@@H:24]4[CH2:28][CH2:29][CH2:30][C@@H:23]34)[N:19]([CH2:31][C@H:32]3[CH2:37][CH2:36][C@H:35]([CH3:38])[CH2:34][CH2:33]3)[C:4]=2[C:5]([C:12]2[CH:13]=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=2)=[N:6][C:7]=1[C:8](=[N:10][OH:11])[NH2:9].[C:39](N1C=CN=C1)(N1C=CN=C1)=[O:40].N12CCCN=C1CCCCC2>C(#N)C>[Cl:1][C:2]1[C:3]2[N:21]=[C:20]([N:22]3[CH2:27][CH2:26][O:25][C@@H:24]4[CH2:28][CH2:29][CH2:30][C@@H:23]34)[N:19]([CH2:31][C@H:32]3[CH2:33][CH2:34][C@H:35]([CH3:38])[CH2:36][CH2:37]3)[C:4]=2[C:5]([C:12]2[CH:13]=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=2)=[N:6][C:7]=1[C:8]1[NH:9][C:39](=[O:40])[O:11][N:10]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 178461240HCID 178461240, compound

Product 1

HCID 178461238HCID 178461238, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 7-chloro-4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-N′-hydroxy-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carboximidamide (33.3 mg, 0.06 mmol) in acetonitrile (2 mL) were added 1,1′-carbonyldiimidazole (19.3 mg, 0.119 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.036 mL, 0.238 mmol). The reaction was stirred at room temperature for 1 hour and then concentrated. The residue was purified by mass triggered reverse phase HPLC (C-18) eluting with acetonitrile/water+0.1% TFA to afford 3-{7-chloro-4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one (TFA salt). MS ESI calc'd for C28H31Cl2N7O3 [M+H]+=584. found=584. 1H NMR (600 MHz, DMSO-d6) δ 12.74 (s, 1H), 8.92 (d, J=1.2 Hz, 1H), 8.80 (d, J=2.4 Hz, 1H), 8.46 (m, 1H), 3.94 (d, J=9.6 Hz, 1H), 3.77-3.86 (m, 2H), 3.56-3.62 (m, 2H), 3.39 (m, 1H), 3.05 (m, 1H), 2.87 (m, 1H), 2.31 (m, 1H), 1.86 (m, 1H), 1.71 (m, 1H), 1.51-1.64 (m, 2H), 1.32-1.41 (m, 2H), 1.12 (m, 1H), 1.04 (m, 1H), 0.81 (m, 1H), 0.65-0.74 (m, 6H), 0.46 (m, 1H), 0.30-0.42 (m, 2H).

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by mass triggered reverse phase HPLC (C-18)
  3. washeluting with acetonitrile/water+0.1% TFA

Sources & evidence

ORD record
ord-397b591c5c5246ab8e0ccf1ee7885539
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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