Pivalic acid → HCID 178439376, 화합물

HRID 81240

반응식

HRID 81240 반응식
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

참가 물질

8

반응물 5

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

생성물 1

HCID 178439376HCID 178439376, 화합물

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

반응 조건

온도
50 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-a9812673d4c24bb4ac6c8d34feb97f52
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846657B2

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