Acetonitrile → 2-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(pyrimidin-2-yl)azetidin-3-yl)acetonitrile

HRID 1853017노트

반응식

HRID 1853017 반응식
Cl.[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:15]=[N:16][N:17]([C:19]4([CH2:23][C:24]#[N:25])[CH2:22][NH:21][CH2:20]4)[CH:18]=3)[N:11]3[CH:26]=[CH:27][N:28]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1.C(#N)C.C([O-])([O-])=O.[K+].[K+].Br[C:39]1[N:44]=[CH:43][CH:42]=[CH:41][N:40]=1>CCOC(C)=O>[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:15]=[N:16][N:17]([C:19]4([CH2:23][C:24]#[N:25])[CH2:22][N:21]([C:39]5[N:44]=[CH:43][CH:42]=[CH:41][N:40]=5)[CH2:20]4)[CH:18]=3)[N:11]3[CH:26]=[CH:27][N:28]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1

참가 물질

6

반응물 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 783452-BromopyrimidineHCID 674570102-(3-(4-(7-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochloride

생성물 1

HCID 674583172-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(pyrimidin-2-yl)azetidin-3-yl)acetonitrile수율 20.2%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

반응 조건

온도
45 °C

실험 절차

To a solution of 2-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochloride (Example 62; 30 mg, 0.069 mmol) in acetonitrile (690 μL, 0.069 mmol) was added K2CO3 (38 mg, 0.28 mmol) and 2-bromopyrimidine (12 mg, 0.076 mmol). The reaction mixture was heated to 45° C. for 3 days. After diluting in EtOAc, the mixture was washed with water and brine. The organic layer was dried with MgSO4, filtered and concentrated in vacuo to a clear colorless oil. The oil was purified by reverse phase HPLC using 0-100% acetonitrile/water gradient to afford 2-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(pyrimidin-2-yl)azetidin-3-yl)acetonitrile (6.1 mg, 20% yield) as a white solid. MS (apci) m/z=438.2 (M+H).

후처리

  1. washthe mixture was washed with water and brine
  2. dry with materialThe organic layer was dried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo to a clear colorless oil
  5. customThe oil was purified by reverse phase

출처 및 근거

ORD 기록
ord-9be92f2e009946708f8a2c1d101e16b3
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962596B2

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