Sodium Bicarbonate → US10023592, Example 252

HRID 518459ノート

反応式

HRID 518459 の反応式
Br[C:2]1[C:3]2[CH:12]=[CH:11][O:10][C:4]=2[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[CH:13]1([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH2:27][CH3:28])(=[O:26])=[O:25])=[CH:20][C:19]=2B2OC(C)(C)C(C)(C)O2)[CH2:15][CH2:14]1.C([O-])(O)=O.[Na+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:13]1([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH2:27][CH3:28])(=[O:26])=[O:25])=[CH:20][C:19]=2[C:2]2[C:3]3[CH:12]=[CH:11][O:10][C:4]=3[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[CH2:14][CH2:15]1

参加物

6

反応物 3

HCID 516892Sodium BicarbonateHCID 896575182-[2-(Cyclopropylmethoxy)-5-(ethylsulfonyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 1180214004-Bromo-6-methylfuro[2,3-c]pyridin-7-one

生成物 1

HCID 118021538US10023592, Example 252収率 25%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
80 °C

実験手順

A mixture of the title compound of step 2 (150 mg, 0.66 mmol), 2-[2-(cyclopropylmethoxy)-5-ethylsulfonylphenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (336 mg, 1.0 mmol), NaHCO3 (167 mg, 1.99 mmol), Pd(dppf)Cl2 (35 mg, 0.048 mmol) in dioxane/H2O (10 mL/2.5 mL) was bubbled with argon for 5 min. The sealed vial was stirred at 80° C. for 18 h. The reaction mixture was concentrated, treated with DCM (30 mL), washed with water (30 mL) and brine (30 mL), dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue was purified by prep-HPLC to give the title compound (63 mg, 25%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 7.90-7.86 (m, 2H), 7.75 (d, J=1.6 Hz, 1H), 7.31 (s, 1H), 7.09 (d, J=8.4 Hz, 1H), 6.57 (d, J=1.6 Hz, 1H), 3.95 (d, J=6.8 Hz, 2H), 3.74 (s, 3H), 3.18-3.12 (q, J=7.6 Hz, 2H), 1.34 (t, J=7.6 Hz, 3H), 1.16-1.15 (m, 1H), 0.61-0.55 (m, 2H), 0.31-0.27 (m, 2H). LCMS (M+H)+=388.

後処理

  1. customwas bubbled with argon for 5 min
  2. concentrationThe reaction mixture was concentrated
  3. additiontreated with DCM (30 mL)
  4. washwashed with water (30 mL) and brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by prep-HPLC

出典と根拠

ORDレコード
ord-18aab0c172994cd5a0197408c39551c8
出典データセット
uspto-grants-2015_08
特許番号
US09115114B2

反応ノート

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