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Dichloromethane → HCID 178423523、化合物

HRID 1525484
ノート
印刷プレビュー

反応式

HRID 1525484 の反応式
FC(F)(F)C(O)=O.[CH3:8][C:9]1[CH:14]=[C:13]([C:15]2[N:19](C3CCCCO3)[CH:18]=[N:17][N:16]=2)[CH:12]=[CH:11][C:10]=1[C:26]1[N:31]=[C:30]2[NH:32][C:33]3([CH2:38][CH2:37]3)[C:34](=[O:36])[NH:35][C:29]2=[N:28][CH:27]=1.CC1(C)C(=O)NC2=NC=C(C3C=CC(C4NC=NN=4)=CC=3C)N=C2N1CCC1CCOCC1.BrC1N=C2NC3(CC3)C(=O)NC2=NC=1.ClCCl.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].C(O)(C)C.O1CCOCC1>[CH3:8][C:9]1[CH:14]=[C:13]([C:15]2[NH:19][CH:18]=[N:17][N:16]=2)[CH:12]=[CH:11][C:10]=1[C:26]1[N:31]=[C:30]2[NH:32][C:33]3([CH2:37][CH2:38]3)[C:34](=[O:36])[NH:35][C:29]2=[N:28][CH:27]=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

9

反応物 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 666081077'-(2-Methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-1'H-spiro[cyclopropane-1,2'-pyrazino[2,3-b]pyrazin]-3'(4'H)-one trifluoroacetateHCID 866446477'-bromo-1'H-spiro[cyclopropane-1,2'-pyrazino[2,3-b]pyrazin]-3'(4'H)-oneHCID 178423524HCID 178423524、化合物

生成物 1

HCID 178423523
HCID 178423523、化合物
収率 38%

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 3776Isopropanol溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

7′-(2-Methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-1′H-spiro[cyclopropane-1,2′-pyrazino[2,3-b]pyrazin]-3′(4′H)-one Trifluoroacetate. 3-(3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazole (See Example 2. C) (0.201 g, 0.545 mmol), 7′-bromo-1′H-spiro[cyclopropane-1,2′-pyrazino[2,3-b]pyrazin]-3′(4′H)-one (0.139 g, 0.545 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.045 g, 0.054 mmol), sodium carbonate (1 M in water, 1.635 mL, 1.635 mmol), 1,4-dioxane (1.2 mL) and isopropanol (0.4 mL) were combined in a sealable vessel with a stirbar. The system was purged with nitrogen. The resulting mixture was sealed, stirred vigorously and heated at 100° C. for 1 h. The resulting mixture was diluted with water and extracted three times with dichloromethane. The combined organics were concentrated under reduced pressure. The residue was taken up in DMSO and methanol, filtered and purified using reverse-phase preparatory HPLC (20-70% acetonitrile+0.1% TFA in water+0.1% TFA, over 30 min). Fractions containing the desired product were combined and the solvent removed under reduced pressure. The residue was dried under high vacuum to give the desired product (0.109 g, 0.205 mmol, 38% yield) as an orange solid. MS (ESI) m/z 418.4 [M+1]+.

後処理

  1. customThe system was purged with nitrogen
  2. customThe resulting mixture was sealed
  3. additionThe resulting mixture was diluted with water
  4. extractionextracted three times with dichloromethane
  5. concentrationThe combined organics were concentrated under reduced pressure
  6. filtrationmethanol, filtered
  7. custompurified
  8. customreverse-phase preparatory HPLC (20-70% acetonitrile+0.1% TFA in water+0.1% TFA, over 30 min)
  9. additionFractions containing the desired product
  10. customthe solvent removed under reduced pressure
  11. customThe residue was dried under high vacuum

出典と根拠

ORDレコード
ord-8729cecfa6ab4fb1a69c3d1a91777551
出典データセット
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09079900B2

反応ノート

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