Pivalic acid → 4-methyl-6-(1,3-thiazol-5-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine

HRID 2402370노트

반응식

HRID 2402370 반응식
C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.Br[C:27]1[N:32]=[C:31]([NH:33][C:34]2[CH:39]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:37]=[CH:36][N:35]=2)[CH:30]=[C:29]([CH3:44])[CH:28]=1.[S:45]1[CH:49]=[CH:48][N:47]=[CH:46]1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C(C)(C)C>CC(N(C)C)=O.[CH2-]C=C.[CH2-]C=C.Cl[Pd+].Cl[Pd+]>[CH3:44][C:29]1[CH:28]=[C:27]([C:49]2[S:45][CH:46]=[N:47][CH:48]=2)[N:32]=[C:31]([NH:33][C:34]2[CH:39]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:37]=[CH:36][N:35]=2)[CH:30]=1

참가 물질

8

반응물 5

HCID 6417Pivalic acidHCID 9256ThiazoleHCID 11430Potassium CarbonateHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 86680795HCID 86680795, 화합물

생성물 1

HCID 709773814-methyl-6-(1,3-thiazol-5-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine수율 43.2%

시약·촉매·용매 2

HCID 61538Palladium, di-mu-chlorobis(eta3-2-propenyl)di-촉매HCID 31374Dimethylacetamide용매2회

실험 절차

In a dry flask, allylpalladium(II) chloride dimer (1.333 g, 3.64 mmol) and butyldiadamantylphosphine (5.23 g, 14.57 mmol) were taken-up in degassed dimethylacetamide (50 mL). The vessel was evacuated and backfilled with argon (3 times), and then stirred at rt for 10 minutes. Additional degassed dimethylacetamide (50 mL), 6-bromo-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine (12.1 g, 36.4 mmol), thiazole (10.36 mL, 146 mmol), potassium carbonate (15.11 g, 109 mmol), and pivalic acid (6.34 mL, 54.6 mmol) were added. The vessel was evacuated and backfilled with argon (3 times) and stirred under argon at 130° C. overnight. The reaction mixture was then diluted with EtOAc (500 mL), cooled to rt, filtered through Celite®, and concentrated. Water was added to the crude product mixture and the resulting precipitate was collected via filtration and subjected to silica gel flash chromatography (ethyl acetate-hexanes). Purification yielded 4-methyl-6-(1,3-thiazol-5-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine (5.29 g, 15.72 mmol, 43% yield) as a yellow solid. MS ESI calcd for C15H11F3N4S [M+H]+ 337, found 337. 1H NMR (600 MHz, DMSO) δ 10.21 (s, 1H), 9.14 (s, 1H), 8.59 (s, 1H), 8.52 (s, 1H), 8.47 (d, J=5.1 Hz, 1H), 7.43 (s, 1H), 7.20 (d, J=5.1 Hz, 1H), 7.11 (s, 1H), 2.30 (s, 3H) ppm.

후처리

  1. customThe vessel was evacuated
  2. additionwere added
  3. customThe vessel was evacuated
  4. stirringstirred under argon at 130° C. overnight
  5. additionThe reaction mixture was then diluted with EtOAc (500 mL)
  6. temperaturecooled to rt
  7. filtrationfiltered through Celite®
  8. concentrationconcentrated
  9. additionWater was added to the crude product mixture
  10. filtrationthe resulting precipitate was collected via filtration
  11. customPurification

출처 및 근거

ORD 기록
ord-09adde890d4b42e1b1d81aa2375480a8
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08796310B2

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