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

HRID 1853014노트

반응식

HRID 1853014 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.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:53][C:54]([F:60])([F:59])[CH2:55][C:56](O)=[O:57].CCN(C(C)C)C(C)C>CN(C=O)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:56](=[O:57])[CH2:55][C:54]([F:60])([F:59])[F:53])[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

7

반응물 4

HCID 81531DiisopropylethylamineHCID 27779723,3,3-Trifluoropropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 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 674550662-(3-(4-(7-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(3,3,3-trifluoropropanoyl)azetidin-3-yl)acetonitrile수율 59%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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, 50.0 mg, 0.116 mmol) and HATU (52.8, 0.139 mmol) in dry DMF (0.50 mL) was added 3,3,3-trifluoropropanoic acid (19.3 mg, 0.150 mmol) and the mixture was stirred at ambient temperature for 2 minutes. DIEA (80.6 μL, 0.463 mmol) was added and the resulting homogeneous solution was stirred at ambient temperature for 18 hours. The reaction mixture was added to H2O (5.0 mL) and extracted with EtOAc. The combined extracts were washed with H2O, saturated aqueous NaHCO3 and dried over MgSO4. The solution was eluted through a silica gel column eluting with EtOAc then with 10% MeOH/EtOAc. The 10% MeOH/EtOAc pool was concentrated to give the title compound (32 mg, 59% yield) as a white solid. MS (apci) m/z=470.2 (M+H).

후처리

  1. stirringthe resulting homogeneous solution was stirred at ambient temperature for 18 hours
  2. extractionextracted with EtOAc
  3. washThe combined extracts were washed with H2O, saturated aqueous NaHCO3
  4. dry with materialdried over MgSO4
  5. washThe solution was eluted through a silica gel column
  6. washeluting with EtOAc
  7. concentrationThe 10% MeOH/EtOAc pool was concentrated

출처 및 근거

ORD 기록
ord-0ed19fa73d414931b213194c0fb5762d
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962596B2

반응 노트

불러오는 중…