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Sodium Carbonate → 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(pyrimidin-5-yl)nicotinamide

HRID 924125
ノート
印刷プレビュー

反応式

HRID 924125 の反応式
[Cl:1][C:2]1[C:21](I)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([Cl:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.[N:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>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].COCCOC>[Cl:1][C:2]1[C:21]([C:27]2[CH:28]=[N:23][CH:24]=[N:25][CH:26]=2)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([Cl:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 867026266-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide

生成物 1

HCID 899064746-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(pyrimidin-5-yl)nicotinamide

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
触媒
HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
90 °C

実験手順

6-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide (Stage 247.2, 8 g, 17.43 mmol), pyrimidine-5-boronic acid (4.55 g, 34.9 mmol), PdCl2(dppf) (0.638 g, 0.871 mmol), Na2CO3 (26.1 mL of 2 M, 52.3 mmol), and DME (110 mL) were added to a vial, which was sealed, evacuated/purged with argon and the RM was stirred at 90° C. for 20 h. The RM was dissolved in EtOAc (200 mL), washed with water, dried over Na2SO4 and the solvent was evaporated off under reduced pressure. The residue was purified by flash chromatography (Silica gel column, 750 g, EtOAc/n-hexane 1:1) and recrystallized from EtOAc/iPr2O to give the title product as a pink solid. HPLC (Condition 10) tR=6.77 min, UPLC-MS (Condition 3) tR=1.05 min, m/z=409.0/411.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 6.59 (d, J=8.60 Hz, 2H) 7.07 (d, J=8.99 Hz, 2H) 7.75 (d, J=1.95 Hz, 1H) 8.18-8.24 (m, 1H) 8.28 (s, 2H) 8.50 (s, 1H) 9.88 (s, 1H).

後処理

  1. customwas sealed
  2. customevacuated/purged with argon
  3. dissolutionThe RM was dissolved in EtOAc (200 mL)
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. customthe solvent was evaporated off under reduced pressure
  7. customThe residue was purified by flash chromatography (Silica gel column, 750 g, EtOAc/n-hexane 1:1)
  8. customrecrystallized from EtOAc/iPr2O

出典と根拠

ORDレコード
ord-9d6b9ef246b149d09b85a751ff11fa21
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09278981B2

反応ノート

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