Sodium Bicarbonate → 1-(2-Fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3-methoxy-3-methylbutyl)urea

HRID 522738ノート

反応式

HRID 522738 の反応式
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][C:3]=1[NH:18][C:19]([NH:21][CH2:22][CH2:23][C:24]([O:27][CH3:28])([CH3:26])[CH3:25])=[O:20].FC(F)(F)S(O[C:35]1[C:46]([CH3:47])=[N:45][C:38]2[N:39]=[C:40]([NH:43][CH3:44])[N:41]=[CH:42][C:37]=2[CH:36]=1)(=O)=O.C([O-])(O)=O.[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:35]2[C:46]([CH3:47])=[N:45][C:38]3[N:39]=[C:40]([NH:43][CH3:44])[N:41]=[CH:42][C:37]=3[CH:36]=2)=[CH:4][C:3]=1[NH:18][C:19]([NH:21][CH2:22][CH2:23][C:24]([O:27][CH3:28])([CH3:25])[CH3:26])=[O:20]

参加物

7

反応物 3

HCID 516892Sodium BicarbonateHCID 898095047-Methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonateHCID 898154411-(2-Fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(3-methoxy-3-methylbutyl)urea

生成物 1

HCID 1180360791-(2-Fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3-methoxy-3-methylbutyl)urea収率 21.1%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒2 回HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
55 °C

実験手順

Combine 1-(2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(3-methoxy-3-methylbutyl)urea (0.17 g, 0.431 mmol), 7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate (0.139 g, 0.431 mmol) and NaHCO3 (0.109 g, 1.293 mmol) in dioxane (6 mL) and H2O (1.5 mL). Sparge the mixture with argon. Treat with tetrakis(triphenylphosphine)palladium (0.025 g, 0.022 mmol), sparge again with argon and heat at 55° C. overnight. Add an additional portion of tetrakis(triphenylphosphine)palladium (25 mg, 0.022 mmol) and heat at 65° C. overnight. Cool the mixture to RT, remove solids by filtration, and wash solids with dioxane. Combine filtrates, dilute with EtOAc, wash with saturated NaHCO3 and brine, dry over Na2SO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex). Dissolve in DCM, wash with saturated NaHCO3 and brine, dry over Na2SO4, concentrate to dryness. Treat with 1:1 MeCN/H2O, freeze in −78° C. bath and lyophilize to obtain the title compound (40 mg, 21% yield) as a pale yellow solid. MS (ESI) m/z: 441.2 (M+1).

後処理

  1. customSparge the mixture with argon
  2. customsparge again with argon
  3. temperatureheat at 65° C. overnight
  4. temperatureCool the mixture to RT
  5. customremove solids
  6. filtrationby filtration
  7. washwash solids with dioxane
  8. additionCombine filtrates, dilute with EtOAc
  9. washwash with saturated NaHCO3 and brine
  10. dry with materialdry over Na2SO4
  11. concentrationconcentrate to dryness
  12. custompurify via silica gel chromatography (EtOAc/Hex)
  13. dissolutionDissolve in DCM
  14. washwash with saturated NaHCO3 and brine
  15. dry with materialdry over Na2SO4
  16. concentrationconcentrate to dryness
  17. additionTreat with 1:1 MeCN/H2O, freeze in −78° C. bath

出典と根拠

ORDレコード
ord-033f7cf20eb84575a3835f21964c211c
出典データセット
uspto-grants-2016_05
特許番号
US09334267B2

反応ノート

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