1,1'-Carbonyldiimidazole → HCID 178483041, compound

HRID 81272Notes

Reaction equation

HRID 81272 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:11]2[C:16]3[N:17]([CH2:29][C@H:30]4[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]4)[C:18]([N:20]4[CH2:25][CH2:24][O:23][C@@H:22]5[CH2:26][CH2:27][CH2:28][C@@H:21]45)=[N:19][C:15]=3[CH:14]=[C:13]([C:37](=[NH:40])[NH:38][OH:39])[N:12]=2)[C:5]([N:8]([CH3:10])[CH3:9])=[N:6][CH:7]=1.[C:41](N1C=CN=C1)(N1C=CN=C1)=[O:42].N1(C2CCCCCCCCCC2)CCCN=CCCCCC1>C(#N)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:11]2[C:16]3[N:17]([CH2:29][C@H:30]4[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]4)[C:18]([N:20]4[CH2:25][CH2:24][O:23][C@@H:22]5[CH2:26][CH2:27][CH2:28][C@@H:21]45)=[N:19][C:15]=3[CH:14]=[C:13]([C:37]3[NH:40][C:41](=[O:42])[O:39][N:38]=3)[N:12]=2)[C:5]([N:8]([CH3:9])[CH3:10])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 1296629601,8-Diazabicycloundec-7eneHCID 178483044HCID 178483044, compound

Product 1

HCID 178483041HCID 178483041, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[5-chloro-2-(dimethylamino)pyridin-3-yl]-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-N-hydroxy-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carboximidamide (racemic, 22 mg, 0.075 mmol) and 1,1′-carbonyldiimidazole (12 mg, 0.07 mmol) in acetonitrile (1 mL) was added 1,8-diazabicycloundec-7-ene (23 mg, 0.15 mmol). The reaction was stirred at room temperature for 18 hours. The reaction was then diluted with CH2Cl2 and washed with water. The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified on a silica gel column (0 to 10% MeOH/CH2Cl2) to afford 3-{4-[5-chloro-2-(dimethylamino)pyridin-3-yl]-2-[(trans)-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 (racemic). NMR shows 8:2 mixture of rotamers, 1H NMR (400 MHz, CD3OD) (for major rotamer) δ 8.27 (d, J=2.8 Hz, 1H), 8.12 (s, 1H), 7.98 (d, J=2.8 Hz, 1H), 3.76-4.04 (m, 3H), 3.35-3.51 (m, 3H), 3.13 (m, 1H), 2.98 (m, 1H), 2.53 (s, 6H), 2.34 (m, 1H), 1.64-1.77 (m, 3H), 1.44-1.56 (m, 3H), 1.12-1.24 (m, 3H), 0.71-0.84 (m, 7H), 0.50-0.62 (m, 2H). MS ES calc'd. for C30H37ClN8O3 [M+H]+ 593. found 593

Workup

  1. washwashed with water
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified on a silica gel column (0 to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-3643861f90dc4ab5a8c10a3d3a497ac1
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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