Acetic Acid → HCID 178482970, compound

HRID 81249Notes

Reaction equation

HRID 81249 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]([N:34]([CH3:36])[CH3:35])=C(C#N)[N:9]=2)[CH:5]=[N:6][CH:7]=1.[OH-].[Na+].[CH3:41][C:42]([OH:44])=[O:43].CS(C)=O>CCO>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:26][C@H:27]4[CH2:28][CH2:29][C@H:30]([CH3:33])[CH2:31][CH2:32]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]([N:34]([CH3:35])[CH3:36])=[C:41]([C:42]([OH:44])=[O:43])[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 679Dimethyl SulfoxideHCID 14798Sodium HydroxideHCID 178482958HCID 178482958, compound

Product 1

HCID 178482970HCID 178482970, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of 4-(5-chloropyridin-3-yl)-7-(dimethylamino)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (31.8 mg, 0.06 mmol) in EtOH (1 mL) was added NaOH (0.2 mL of a 5M aq. solution, 1 mmol). The reaction was heated at 70° C. for 60 hours and then cooled to room temperature. HOAc (60 μL, 1 mmol) was added followed by DMSO (1.5 mL). After sonication and filtration to remove solids, the filtrate was purified by mass triggered reverse phase HPLC(C-18) eluting with acetonitrile/water+0.1% TFA to afford 4-(5-chloropyridin-3-yl)-7-(dimethylamino)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carboxylic acid (TFA salt). MS ESI calc'd for C29H37ClN6O3 [M+H]+=553. found=553. 1H NMR (600 MHz, DMSO-d6) δ 8.75-8.77 (m, 2H), 8.27 (m, 1H), 3.93 (dd, J=12.0, 1.8 Hz, 1H), 3.75-3.81 (m, 2H), 3.47-3.52 (m, 2H), 3.38 (m, 1H), 3.15 (s, 6H), 3.03 (m, 1H), 2.81 (m, 1H), 2.26 (m, 1H), 1.85 (m, 1H), 1.69 (m, 1H), 1.51-1.63 (m, 2H), 1.31-1.41 (m, 2H), 1.13 (m, 1H), 1.05 (m, 1H), 0.83 (m, 1H), 0.64-0.73 (m, 6H), 0.34-0.46 (m, 3H).

Workup

  1. temperaturecooled to room temperature
  2. customAfter sonication and filtration
  3. customto remove solids
  4. customthe filtrate was purified by mass triggered reverse phase
  5. washHPLC(C-18) eluting with acetonitrile/water+0.1% TFA

Sources & evidence

ORD record
ord-75c1a4a11c8e41be942444d5cb24f548
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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