3-Fluoro-2-pyridinecarboxaldehyde → HCID 178461203, 화합물

HRID 81227

반응식

HRID 81227 반응식
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([Cl:14])[CH:13]=2)[C:5]2[N:15]([CH2:18][C@H:19]3[CH2:24][CH2:23][C@H:22]([CH3:25])[CH2:21][CH2:20]3)[CH:16]=[N:17][C:4]=2[CH:3]=1.[Cl-].[Li+].CC1(C)CCCC(C)(C)N1[Mg]Cl.[F:40][C:41]1[C:42]([CH:47]=[O:48])=[N:43][CH:44]=[CH:45][CH:46]=1>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([Cl:14])[CH:13]=2)[C:5]2[N:15]([CH2:18][C@H:19]3[CH2:24][CH2:23][C@H:22]([CH3:25])[CH2:21][CH2:20]3)[C:16]([CH:47]([C:42]3[C:41]([F:40])=[CH:46][CH:45]=[CH:44][N:43]=3)[OH:48])=[N:17][C:4]=2[CH:3]=1

참가 물질

5

반응물 3

HCID 113440173-Fluoro-2-pyridinecarboxaldehydeHCID 178424953HCID 178424953, 화합물HCID 178461250HCID 178461250, 화합물

생성물 1

HCID 178461203HCID 178461203, 화합물

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

To a stirred solution of 6-chloro-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (Preparative Example 3.1, Step 1) (1.2 g, 3.19 mmol) in THF (20 mL) was added 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex (Aldrich, 1M in THF/toluene) (5.11 mL, 5.11 mmol) at −78° C., and the reaction was stirred at −78° C. for 2 hours under a nitrogen atmosphere. 3-fluoropicolinaldehyde (1.1 g, 9.59 mmol) dissolved in THF (4.0 mL) was added dropwise at −78° C., and the reaction was stirred for an additional 2 hours at −78° C. The reaction was quenched with aqueous saturated NH4Cl solution (50 mL) and extracted with ethyl acetate (2×40 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated. Purification of the residue on a silica gel column (0 to 100% EtOAc/hexanes) afforded {6-chloro-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridin-2-yl}(3-fluoropyridin-2-yl)methanol. MS APCl calcd. for C25H24Cl2FN5O [M+H]+ 500. found 500.

후처리

  1. additionwas added dropwise at −78° C.
  2. stirringthe reaction was stirred for an additional 2 hours at −78° C
  3. customThe reaction was quenched with aqueous saturated NH4Cl solution (50 mL)
  4. extractionextracted with ethyl acetate (2×40 mL)
  5. washThe combined organic extracts were washed with brine (20 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the residue on a silica gel column (0 to 100% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-c4e04b20d00b456a88db4496f9bbdc08
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846657B2

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