Pivalic acid → HCID 178439376, compound

HRID 81240

Reaction equation

HRID 81240 reaction equation
C12(P(C34CC5CC(CC(C5)C3)C4)CCCC)CC3CC(CC(C3)C1)C2.[Cl:26][C:27]1[CH:28]=[C:29]([C:33]2[C:38]3[N:39]([CH2:42][C@H:43]4[CH2:48][CH2:47][C@H:46]([CH3:49])[CH2:45][CH2:44]4)[CH:40]=[N:41][C:37]=3[CH:36]=[C:35]([C:50]#[N:51])[N:34]=2)[CH:30]=[N:31][CH:32]=1.Br[C:53]1[CH:58]=[C:57]([CH:59]([CH3:61])[CH3:60])[CH:56]=[CH:55][N:54]=1.[F-].[Cs+].C(O)(=O)C(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[Cl:26][C:27]1[CH:28]=[C:29]([C:33]2[C:38]3[N:39]([CH2:42][C@H:43]4[CH2:48][CH2:47][C@H:46]([CH3:49])[CH2:45][CH2:44]4)[C:40]([C:53]4[CH:58]=[C:57]([CH:59]([CH3:61])[CH3:60])[CH:56]=[CH:55][N:54]=4)=[N:41][C:37]=3[CH:36]=[C:35]([C:50]#[N:51])[N:34]=2)[CH:30]=[N:31][CH:32]=1

Participants

8

Reactant 5

HCID 6417Pivalic acidHCID 25953Cesium fluorideHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 457879862-Bromo-4-isopropylpyridineHCID 178461253HCID 178461253, compound

Product 1

HCID 178439376HCID 178439376, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A vial equipped with a stir bar was charged with di(1-adamantyl)-n-butylphosphine (cataCXium A, Strem) (143.2 mg, 0.40 mmol) and palladium acetate (45 mg, 0.20 mmol). Dioxane (2.5 mL) was added, and the mixture was degassed with N2. The vial was then sealed and heated at 50° C. for 30 minutes. The catalyst slurry was then cooled back to room temperature, and 1.5 mL of this catalyst slurry was added via syringe to a second vial equipped with a stir bar and containing 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1, Step 2;100 mg, 0.273 mmol), 2-bromo-4-isopropylpyridine (109 mg, 0.547 mmol; purchased from Combiphos), cesium fluoride (125 mg, 0.82 mmol), and pivalic acid (36.3 mg, 0.355 mmol). The reaction was degassed with N2 for 2 minutes, and then the vial was sealed and heated at 110° C. for 20 hours. The reaction was then cooled to room temperature, diluted with hexanes (2 mL) and CH2Cl2 (2 mL), and loaded directly onto a silica gel column. Purification with 0 to 75% EtOAc/hexanes afforded 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[4-(propan-2-yl)pyridin-2-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C28H29ClN6 [M+H]+=485. found=485.

Workup

  1. customA vial equipped with a stir bar
  2. customthe mixture was degassed with N2
  3. customThe vial was then sealed
  4. temperatureThe catalyst slurry was then cooled back to room temperature
  5. addition1.5 mL of this catalyst slurry was added via syringe to a second
  6. customvial equipped with a stir bar
  7. customThe reaction was degassed with N2 for 2 minutes
  8. customthe vial was sealed
  9. temperatureheated at 110° C. for 20 hours
  10. temperatureThe reaction was then cooled to room temperature
  11. additiondiluted with hexanes (2 mL) and CH2Cl2 (2 mL)
  12. customPurification with 0 to 75% EtOAc/hexanes

Sources & evidence

ORD record
ord-a9812673d4c24bb4ac6c8d34feb97f52
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Linked notes

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