Dimethyl Sulfoxide → HCID 178510200、化合物

HRID 1623305

反応式

HRID 1623305 の反応式
[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

参加物

5

反応物 3

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

生成物 1

HCID 178510200HCID 178510200、化合物収率 80.1%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
105 °C

実験手順

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, 2H) 1.50-1.64 (m, 2H) 2.06-2.22 (m, 4H) 3.08-3.20 (m, 1H) 3.63-3.74 (m, 1H) 4.61 (s, 2H) 6.81 (s, 1H) 6.87 (s, 1H) 6.91-6.99 (m, 1H) 7.02 (s, 1H) 7.04-7.10 (m, 1H) 7.12-7.18 (m, 1H) 7.25-7.36 (m, 1H) 8.00 (s, 1H).

後処理

  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

出典と根拠

ORDレコード
ord-394708aae3084d7e9844b24a7c6f9ac2
出典データセット
uspto-grants-2014_07
特許番号
US08778951B2

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