Sulfuric Acid → HCID 178483043, compound

HRID 81270Notes

Reaction equation

HRID 81270 reaction equation
OS(O)(=O)=O.C[C:7]([N:9](C)C)=O.[Cl:12][C:13]1[CH:14]=[C:15]([C:22]2[C:27]3[N:28]([CH2:40][C@H:41]4[CH2:46][CH2:45][C@H:44]([CH3:47])[CH2:43][CH2:42]4)[C:29]([N:31]4[CH2:36][CH2:35][O:34][C@@H:33]5[CH2:37][CH2:38][CH2:39][C@@H:32]45)=[N:30][C:26]=3[CH:25]=[C:24](Cl)[N:23]=2)[C:16]([N:19]([CH3:21])[CH3:20])=[N:17][CH:18]=1>CC([O-])=O.CC([O-])=O.[Pd+2].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.[Fe+2].[C-]#N.[C-]#N.[Zn+2].[Zn].O>[Cl:12][C:13]1[CH:14]=[C:15]([C:22]2[C:27]3[N:28]([CH2:40][C@H:41]4[CH2:46][CH2:45][C@H:44]([CH3:47])[CH2:43][CH2:42]4)[C:29]([N:31]4[CH2:36][CH2:35][O:34][C@@H:33]5[CH2:37][CH2:38][CH2:39][C@@H:32]45)=[N:30][C:26]=3[CH:25]=[C:24]([C:7]#[N:9])[N:23]=2)[C:16]([N:19]([CH3:20])[CH3:21])=[N:17][CH:18]=1

Participants

9

Reactant 3

HCID 1118Sulfuric AcidHCID 31374DimethylacetamideHCID 178483042HCID 178483042, compound

Product 1

HCID 178483043HCID 178483043, compound

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A vial was charged with H2SO4 (6 mg, 0.005 mmol) and DMA (3 mL) and was degassed with N2 for 3 minutes. Pd(OAc)2 (13.5 mg, 0.005 mmol) and dppf (33.4 mg, 0.005 mmol) were added. The vial was sealed and heated at 80° C. for 30 minutes and then was cooled to room temperature. 1 mL of this solution was added to a second vial containing 5-chloro-3-{6-chloro-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridin-4-yl}-N,N-dimethylpyridin-2-amine (racemic, 81 mg, 0.14 mmol), Zn(CN)2 (7.8 mg, 0.06 mmol) and Zn (1.0 mg, 0.014 mmol) under an atmosphere of N2. The reaction was sealed and heated at 95° C. for 18 hours. Water (5 mL) was added, and the aqueous layer was extracted with EtOAc (2×5 mL). 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 50% EtOAc/hexanes) to afford 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]pyridine-6-carbonitrile (racemic). MS ES calc'd. for C29H38ClN7O [M+H]+ 534. found 534.

Workup

  1. customwas degassed with N2 for 3 minutes
  2. customThe vial was sealed
  3. temperaturewas cooled to room temperature
  4. customThe reaction was sealed
  5. temperatureheated at 95° C. for 18 hours
  6. extractionthe aqueous layer was extracted with EtOAc (2×5 mL)
  7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified on a silica gel column (0 to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-77a1907318f2462eb30b7f9206d3e5d1
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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