Water → HCID 178461233, compound

HRID 1852880Notes

Reaction equation

HRID 1852880 reaction equation
Cl[C:2]1[C:7]2[N:8]([CH2:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]3)[C:9]([N:11]3[CH2:16][CH2:15][O:14][C@@H:13]4[CH2:17][CH2:18][CH2:19][C@@H:12]34)=[N:10][C:6]=2[CH:5]=[C:4]([Cl:28])[N:3]=1.[CH2:29]([O:36][C:37]1[C:42](B(O)O)=[CH:41][C:40]([Cl:46])=[CH:39][N:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[Na+].[Na+].O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCOC(C)=O>[CH2:29]([O:36][C:37]1[C:42]([C:2]2[C:7]3[N:8]([CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]4)[C:9]([N:11]4[CH2:16][CH2:15][O:14][C@@H:13]5[CH2:17][CH2:18][CH2:19][C@@H:12]45)=[N:10][C:6]=3[CH:5]=[C:4]([Cl:28])[N:3]=2)=[CH:41][C:40]([Cl:46])=[CH:39][N:38]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 53216265(2-(Benzyloxy)-5-chloropyridin-3-yl)boronic acidHCID 178461234HCID 178461234, compound

Product 1

HCID 178461233HCID 178461233, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

4,6-dichloro-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (racemic, 460 mg, 1.08 mmol), (2-(benzyloxy)-5-chloropyridin-3-yl)boronic acid (purchased from Combi-Blocks Inc.; 372 mg, 1.41 mmol) and 2M aqueous Na2CO3 (5 mL, 10 mmol) were added to degassed 1,2-dimethoxyethane (15 mL), followed by the addition of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (159 mg, 0.2 mmol). The reaction was heated at 90° C. for 6 hours. Water and EtOAc were added. The aqueous layer was extracted several times with EtOAc. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified on a silica gel column (0 to 30% EtOAc/hexanes) to afford 4-[2-(benzyloxy)-5-chloropyridin-3-yl]-6-chloro-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (racemic). MS ES calc'd. for C33H37Cl2N5O2 [M+H]+ 606. found 606.

Workup

  1. customto degassed 1,2-dimethoxyethane (15 mL)
  2. extractionThe aqueous layer was extracted several times with EtOAc
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a silica gel column (0 to 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e6eea63f338f4c388905fdd2f512a0b2
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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