Sodium Carbonate → 4-[2-Chloro-6-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-4-yl]-phenylamine

HRID 75411

반응식

HRID 75411 반응식
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:14][CH:13]3[O:15][CH:10]([CH2:11][CH2:12]3)[CH2:9]2)[CH:5]=[C:4]([Cl:16])[N:3]=1.CC1(C)C(C)(C)OB([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:3]=[C:4]([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=2)[CH:5]=[C:6]([N:8]2[CH2:14][CH:13]3[O:15][CH:10]([CH2:11][CH2:12]3)[CH2:9]2)[N:7]=1.[Cl:16][C:4]1[CH:5]=[C:6]([N:8]2[CH2:14][CH:13]3[O:15][CH:10]([CH2:11][CH2:12]3)[CH2:9]2)[N:7]=[C:2]([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=2)[N:3]=1

참가 물질

9

반응물 3

HCID 10340Sodium CarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 866658793-(2,6-Dichloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

생성물 2

HCID 866658814-[2-Chloro-6-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-4-yl]-phenylamine수율 16%HCID 86665882HCID 86665882, 화합물수율 15%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
120 °C

실험 절차

In a 2-5 mL microwave vial was placed 3-(2,6-dichloropyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (9, 100 mg, 0.384 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (84 mg, 0.384 mmol) in toluene (1.500 mL) and ethanol (1 mL) to give a light yellow solution. Na2CO3 (2M solution in water) (0.769 mL, 1.538 mmol) was added. The mixture was degassed by bubbling nitrogen through the solution. Pd(PPh3)4 (22.21 mg, 0.019 mmol) was added. The reaction was heated under microwave irradiation at 120° C. for 30 min. The reaction mixture was diluted with ethyl acetate and washed with sat NaHCO3 (2×). The organic layer was dried over MgSO4, filtered and concentrated. The crude product was added to a silica gel column and was eluted with 20-80% ethyl acetate in hexanes. Collected fractions were concentrated to give 4-[2-chloro-6-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-4-yl]-phenylamine (11, 19 mg, 16%) and 4-[4-chloro-6-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-yl]-phenylamine (12, 18 mg, 15%).

후처리

  1. customto give a light yellow solution
  2. customThe mixture was degassed
  3. customby bubbling nitrogen through the solution
  4. washwashed
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionThe crude product was added to a silica gel column
  9. washwas eluted with 20-80% ethyl acetate in hexanes
  10. concentrationCollected fractions were concentrated

출처 및 근거

ORD 기록
ord-71c01940e7fc498786f55807303445eb
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835429B2

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