Dimethylamine → HCID 178482958, compound

HRID 81248Notes

Reaction equation

HRID 81248 reaction equation
Cl[C:2]1[C:3]2[N:19]=[C:18]([N:20]3[CH2:25][CH2:24][O:23][C@@H:22]4[CH2:26][CH2:27][CH2:28][C@@H:21]34)[N:17]([CH2:29][C@H:30]3[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]3)[C:4]=2[C:5]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([Cl:16])[CH:15]=2)=[N:6][C:7]=1[C:8]#[N:9].[F-].[Cs+].[CH3:39][NH:40][CH3:41].CS(C)=O>C1COCC1.CCOC(C)=O>[Cl:16][C:14]1[CH:15]=[C:10]([C:5]2[C:4]3[N:17]([CH2:29][C@H:30]4[CH2:31][CH2:32][C@H:33]([CH3:36])[CH2:34][CH2:35]4)[C:18]([N:20]4[CH2:25][CH2:24][O:23][C@@H:22]5[CH2:26][CH2:27][CH2:28][C@@H:21]45)=[N:19][C:3]=3[C:2]([N:40]([CH3:41])[CH3:39])=[C:7]([C:8]#[N:9])[N:6]=2)[CH:11]=[N:12][CH:13]=1

Participants

7

Reactant 4

HCID 674DimethylamineHCID 679Dimethyl SulfoxideHCID 25953Cesium fluorideHCID 178461239HCID 178461239, compound

Product 1

HCID 178482958HCID 178482958, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A dry vial, under an atmosphere of nitrogen, was charged with 7-chloro-4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 11.2, step 1; 50 mg, 0.095 mmol), CsF (101 mg, 0.666 mmol), dimethylamine (0.476 mL of a 2M solution in THF, 0.952 mmol) and DMSO (1 mL). The vial was sealed and heated to 100° C. for 8 hours. The reaction was cooled to room temperature, diluted with EtOAc (25 mL) and washed with water (5 mL) and brine (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified on a silica gel column with 0 to 100% EtOAc/hexanes 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-carbonitrile. MS ESI calc'd for C29H36ClN7O [M+H]+=534. found=534.

Workup

  1. customThe vial was sealed
  2. temperatureThe reaction was cooled to room temperature
  3. washwashed with water (5 mL) and brine (5 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on a silica gel column with 0 to 100% EtOAc/hexanes

Sources & evidence

ORD record
ord-3018271c384b41a6be8396cc9ac2a2a2
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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