Trifluoroacetic acid → 2-(2-(4-(isopropylsulfonyl)phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)-5-(1H-pyrazol-5-yl)isoindolin-1-one

HRID 627793ノート

反応式

HRID 627793 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([C:12]1[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([S:27]([CH:30]([CH3:32])[CH3:31])(=[O:29])=[O:28])=[CH:23][CH:22]=4)[N:19]=3)[N:14](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH:13]=1)[CH2:5]2.[NH:52]1[C:56](B(O)O)=[CH:55][CH:54]=[N:53]1.C([O-])([O-])=O.[Na+].[Na+].[SiH](CC)(CC)CC.C(O)(C(F)(F)F)=O>O1CCOCC1>[CH:30]([S:27]([C:24]1[CH:23]=[CH:22][C:21]([C:18]2[N:19]=[C:20]3[C:12]([N:6]4[CH2:5][C:4]5[C:8](=[CH:9][CH:10]=[C:2]([C:54]6[NH:53][N:52]=[CH:56][CH:55]=6)[CH:3]=5)[C:7]4=[O:11])=[CH:13][NH:14][C:15]3=[N:16][CH:17]=2)=[CH:26][CH:25]=1)(=[O:28])=[O:29])([CH3:31])[CH3:32]

参加物

7

反応物 5

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 12052TriethylsilaneHCID 112519791H-Pyrazole-5-boronic acidHCID 711436245-Bromo-2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]isoindolin-1-one

生成物 1

HCID 711435972-(2-(4-(isopropylsulfonyl)phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)-5-(1H-pyrazol-5-yl)isoindolin-1-one収率 21.2%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
60 °C

実験手順

5-bromo-2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]isoindolin-1-one (100 mg, 0.1327 mmol), 1H-pyrazol-5-ylboronic acid (17.81 mg, 0.1592 mmol) and Na2CO3 (200 μL of 2 M aqueous solution, 0.40 mmol) combined in 1,4-dioxane (1.5 mL). Mixture de-gassed (×3 vacuum-N2 cycles). Pd(tBu3P)2 (6.782 mg, 0.01327 mmol) added and mixture de-gassed (×3 cycles) then heated overnight at 60° C. Reaction mixture partitioned between DCM and water. Aqueous phase extracted with DCM. Combined organics dried and concentrated. Residue taken up in DCM (2 mL) and Et3SiH (106.0 μL, 0.6635 mmol) then TFA (0.3 mL) added under N2. Mixture stirred for 48 h then concentrated and residue azeotroped with DCM (×3). Residue purified by hplc to give the title compound (14 mg, 21%); 1H NMR (400 MHz, DMSO) 1.22 (6H, d), 3.50 (1H, sep), 5.58 (2H, s), 6.90 (1H, d), 7.83-7.87 (2H, m), 8.00 (2H, d), 8.05 (1H, d), 8.25 (1H, s), 8.53-8.57 (3H, m), 9.11 (1H, s), 12.33 (1H, vbrs), 13.10 (1H, s); MS (ES+) 499.0.

後処理

  1. customMixture de-gassed (×3 vacuum-N2 cycles)
  2. custommixture de-gassed (×3 cycles)
  3. customReaction mixture
  4. custompartitioned between DCM and water
  5. extractionAqueous phase extracted with DCM
  6. customCombined organics dried
  7. concentrationconcentrated
  8. concentrationthen concentrated
  9. customresidue azeotroped with DCM (×3)
  10. customResidue purified by hplc

出典と根拠

ORDレコード
ord-40d60793540b4b5a800d6d2b51f7a5c1
出典データセット
uspto-grants-2016_04
特許番号
US09309250B2

反応ノート

読み込み中…