Dimethylacetamide → HCID 178461235, compound

HRID 81276Notes

Reaction equation

HRID 81276 reaction equation
[CH2:1]([O:8][C:9]1[C:14]([C:15]2[C:20]3[N:21]([CH2:33][C@H:34]4[CH2:39][CH2:38][C@H:37]([CH3:40])[CH2:36][CH2:35]4)[C:22]([N:24]4[CH2:29][CH2:28][O:27][C@@H:26]5[CH2:30][CH2:31][CH2:32][C@@H:25]45)=[N:23][C:19]=3[CH:18]=[C:17](Cl)[N:16]=2)=[CH:13][C:12]([Cl:42])=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[C:44]([N:46](C)C)=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH2:1]([O:8][C:9]1[C:14]([C:15]2[C:20]3[N:21]([CH2:33][C@H:34]4[CH2:39][CH2:38][C@H:37]([CH3:40])[CH2:36][CH2:35]4)[C:22]([N:24]4[CH2:29][CH2:28][O:27][C@@H:26]5[CH2:30][CH2:31][CH2:32][C@@H:25]45)=[N:23][C:19]=3[CH:18]=[C:17]([C:44]#[N:46])[N:16]=2)=[CH:13][C:12]([Cl:42])=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 31374DimethylacetamideHCID 178461233HCID 178461233, compound

Product 1

HCID 178461235HCID 178461235, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

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, 450 mg, 0.74 mmol), zinc cyanide (43 mg, 0.37 mmol) and Pd(PPh3)4 (128 mg, 0.11 mmol) were placed in a dry vial. Degassed DMA (4 mL) was added to the reaction, and the reaction was placed under an atmosphere of Ar, sealed, and heated at 90° C. for 12 hours. The reaction was then cooled to room temperature, and cold water was added slowly. The aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification of the residue on a silica gel column (0 to 50% EtOAc/hexanes) afforded 4-[2-(benzyloxy)-5-chloropyridin-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 as a racemic mixture. The enantiomers were separated on a chiral OD column using 2% IPA/98% heptanes. MS ES calc'd. for C34H37ClN6O2 [M+H]+ 597. found 597.

Workup

  1. customsealed
  2. temperatureThe reaction was then cooled to room temperature
  3. extractionThe aqueous layer was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the residue on a silica gel column (0 to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-84c3c11a6db74a07ac56f749d6a7c3e1
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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