1,1'-Carbonyldiimidazole → HCID 178461241, compound

HRID 81244Notes

Reaction equation

HRID 81244 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:26][C@H:27]4[CH2:32][CH2:31][C@H:30]([CH3:33])[CH2:29][CH2:28]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][C@@H:19]5[CH2:23][CH2:24][CH2:25][C@@H:18]45)=[N:16][C:12]=3[C:11]([F:34])=[C:10]([C:35](=[N:37][OH:38])[NH2:36])[N:9]=2)[CH:5]=[N:6][CH:7]=1.ClC1C2N=C(N3CC[O:63][C@@H:62]4CCC[C@@H]34)N(C[C@H]3CC[C@H](C)CC3)C=2C(C2C=NC=C(Cl)C=2)=NC=1C(=NO)N.C(N1C=CN=C1)(N1C=CN=C1)=O.N12CCCN=C1CCCCC2>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:26][C@H:27]4[CH2:32][CH2:31][C@H:30]([CH3:33])[CH2:29][CH2:28]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][C@@H:19]5[CH2:23][CH2:24][CH2:25][C@@H:18]45)=[N:16][C:12]=3[C:11]([F:34])=[C:10]([C:35]3[NH:36][C:62](=[O:63])[O:38][N:37]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 178461240HCID 178461240, compoundHCID 178461242HCID 178461242, compound

Product 1

HCID 178461241HCID 178461241, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 3:1 mixture of 4-(5-chloropyridin-3-yl)-7-fluoro-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 and 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 mg, 0.06 mmol) in acetonitrile (2 mL) was added 1,1′-carbonyldiimidazole (19.7 mg, 0.122 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.037 mL, 0.244 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 pure 3-{4-(5-chloropyridin-3-yl)-7-fluoro-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 C28H31ClFNγO3 [M+H]+=568. found=568. 1H NMR (600 MHz, DMSO-d6) δ 12.83 (s, 1H), 8.91 (d, J=1.8 Hz, 1H), 8.79 (d, J=2.4 Hz, 1H), 8.43 (m, 1H), 3.94 (d, J=9.6 Hz, 1H), 3.78-3.87 (m, 2H), 3.63 (dd, J=14.4, 3.6 Hz, 1H), 3.56 (d, J=12.6 Hz, 1H), 3.39 (m, 1H), 3.04 (m, 1H), 2.84 (m, 1H), 2.27 (m, 1H), 1.86 (m, 1H), 1.69 (m, 1H), 1.51-1.64 (m, 2H), 1.32-1.41 (m, 2H), 1.12 (m, 1H), 1.04 (m, 1H), 0.80 (m, 1H), 0.63-0.74 (m, 6H), 0.47 (m, 1H), 0.29-0.42 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-d172b552f84e4f18a5441452a9b00a43
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

Loading…