Benzylamine → Benzyl-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-amine

HRID 1186510노트

반응식

HRID 1186510 반응식
Br[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][N:15]=[C:16]([N:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)[C:11]3=[N:10][CH:9]=2)[CH:5]=[CH:4][CH:3]=1.[CH2:24]([NH2:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.CC([O-])(C)C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:24]([NH:31][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][N:15]=[C:16]([N:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)[C:11]3=[N:10][CH:9]=2)[N:7]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

참가 물질

7

반응물 4

HCID 7504BenzylamineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 86670919HCID 86670919, 화합물

생성물 1

HCID 68226504Benzyl-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-amine

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

A mixture of 3-(6-bromo-pyridin-2-yl)-8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazine (from Example 39 supra) (0.187 g, 0.5 mmol), benzylamine (0.075 g, 0.7 mmol), Pd2(dba)3 (30 mg), Davephos (40 mg), NaOtBu (70 mg, 0.73 mmol) in dioxane (20 mL) was bubbled with N2 for several minutes and then heated under N2 at reflux overnight. The solution was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was purified firstly by chromatography (CH2Cl2:CH3OH, 100:1), then by preparative-HPLC to give benzyl-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-amine. (Yield 70 mg, 35%). 1HNMR (300 MHz, CDCl3): δ 8.70 (d, 1H, J=4.5 Hz), 7.88 (s, 1H), 7.51-7.24 (m, 7H), 7.02 (d, 1H, J=7.2 Hz), 6.37 (d, 1H, J=8.1 Hz), 5.03-5.02 (m, 1H), 4.62 (d, 2H, J=3.9 Hz), 4.24 (brs, 4H), 2.61-2.58 (m, 4H), 2.36 (s, 3H). LC-MS: [M+H]+ 400.

후처리

  1. customwas bubbled with N2 for several minutes
  2. temperatureheated under N2
  3. temperatureat reflux overnight
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was purified firstly by chromatography (CH2Cl2:CH3OH, 100:1)

출처 및 근거

ORD 기록
ord-03b643b85d0f4a8aabf8514ca2c19bd9
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08673905B2

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