Dimethyl Sulfoxide → HCID 178510200, 화합물

HRID 1963884

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HRID 1963884 반응식
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[C:13]([C:15]#[N:16])[CH:12]=[C:11]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.CS(C)=O.[C@H:30]1([NH2:37])[CH2:35][CH2:34][C@H:33]([NH2:36])[CH2:32][CH2:31]1>CCOC(C)=O>[NH2:36][C@H:33]1[CH2:34][CH2:35][C@H:30]([NH:37][C:5]2[CH:4]=[C:3]([C:9]3[CH:14]=[C:13]([C:15]#[N:16])[CH:12]=[C:11]([NH:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=4)[N:10]=3)[C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:31][CH2:32]1

참가 물질

5

반응물 3

HCID 679Dimethyl SulfoxideHCID 669369675'-Chloro-2'-fluoro-6-(3-fluorobenzylamino)-2,4'-bipyridine-4-carbonitrileHCID 178511674HCID 178511674, 화합물

생성물 1

HCID 178510200HCID 178510200, 화합물수율 80.1%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
105 °C

실험 절차

To a scintillation vial containing 5′-chloro-2′-fluoro-6-(3-fluorobenzylamino)-2,4′-bipyridine-4-carbonitrile (72 mg, 0.202 mmol) was added DMSO (3 ml) and trans-cyclohexane-1,4-diamine (230 mg, 2.018 mmol). The homogenous yellow reaction mixture was capped and heated to 105° C. in a oil bath for 3 hr. The reaction mixture was diluted with EtOAc and washed with sat NaHCO3, sat NaCl. The organic layer was dried Na2SO4, filtered and concentrated. The crude solid was purified by Prep HPLC and the collected fractions were combined and diluted with EtOAc and neutralized with sat NaHCO3 and then sat NaCl. The organic layer was dried over Na2SO4, filtered and concentrated to afford 2′-(trans-4-aminocyclohexylamino)-5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridine-4-carbonitrile (73 mg, 80%). LCMS (m/z): 451.2 (MH+), retention time=0.70 min. 1H NMR (400 MHz, METHANOL-d4) d ppm 1.34-1.48 (m, 2 H) 1.50-1.64 (m, 2 H) 2.06-2.22 (m, 4 H) 3.08-3.20 (m, 1 H) 3.63-3.74 (m, 1 H) 4.61 (s, 2H) 6.81 (s, 1 H) 6.87 (s, 1 H) 6.91-6.99 (m, 1 H) 7.02 (s, 1H) 7.04-7.10 (m, 1H) 7.12-7.18 (m, 1 H) 7.25-7.36 (m, 1 H) 8.00 (s, 1 H).

후처리

  1. customThe homogenous yellow reaction mixture was capped
  2. washwashed
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude solid was purified by Prep HPLC
  6. additiondiluted with EtOAc and neutralized with sat NaHCO3
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-e136cd7fc61144dabd0acdbd052510ce
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415381B2

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