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Sodium Bicarbonate → 1-Cyclopropyl-3-(4-(6a-methyl-6-oxo-5-(2,2,2-trifluoroethyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl)urea

HRID 1696046
ノート
印刷プレビュー

反応式

HRID 1696046 の反応式
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([F:16])([F:15])[F:14])[C:7](=[O:17])[C:6]3([CH3:22])[CH2:18][O:19][CH2:20][CH2:21][N:5]3[C:4]=2[N:3]=1.[CH:23]1([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][CH:31]=2)=[O:28])[CH2:25][CH2:24]1.C([O-])(O)=O.[Na+]>O1CCOCC1.C1COCC1.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:23]1([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH2:12][C:13]([F:16])([F:15])[F:14])[C:7](=[O:17])[C:6]5([CH3:22])[CH2:18][O:19][CH2:20][CH2:21][N:5]5[C:4]=4[N:3]=3)=[CH:32][CH:31]=2)=[O:28])[CH2:25][CH2:24]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 516892Sodium BicarbonateHCID 44119149N-Cyclopropyl-N'-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 866516012-chloro-6a-methyl-5-(2,2,2-trifluoroethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

生成物 1

HCID 581698181-Cyclopropyl-3-(4-(6a-methyl-6-oxo-5-(2,2,2-trifluoroethyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl)urea収率 50%

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 8028Tetrahydrofuran溶媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 2-chloro-6a-methyl-5-(2,2,2-trifluoroethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (292 mg, 0.868 mmol), 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (446 mg, 1.48 mmol), saturated aqueous NaHCO3 (2 ml) and PdCl2(dppf) (56.7 mg, 0.069 mmol) in 1,4-dioxane (4 ml) was irradiated in microwave at 110° C. for 30 minutes The reaction mixture was diluted with THF and passed through 0.45 μM PTFE syringe filter (washed with small amount of THF). The filtrate was purified by preparative HPLC (eluting with a gradient of 25-50% ACN (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column). The fractions containing the desired product were combined and were evaporated under reduced pressure. Then NaHCO3 aqueous solution was added (in order to adjust the pH to basic) and extracted with EtOAc (THF was added to dissolve the precipitate). The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo to afford the title compound (206 mg, 0.432 mmol, 50% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) ppm 0.37-0.45 (m, 2 H) 0.59-0.69 (m, 2 H) 1.37 (s, 3 H) 2.51-2.60 (m, 1 H) 3.22-3.33 (m, 1 H) 3.55-3.73 (m, 2 H) 3.98-4.11 (m, 2 H) 4.15-4.24 (m, 1 H) 4.80-4.94 (m, 1 H) 4.94-5.11 (m, 1 H) 6.43-6.50 (m, 1 H) 7.46-7.54 (m, 2 H) 8.15-8.23 (m, 2 H) 8.47 (s, 1 H) 8.56 (s, 1 H). MS [M+H] found 477.

後処理

  1. customwas irradiated in microwave at 110° C. for 30 minutes The reaction mixture
  2. custompassed through 0.45 μM PTFE syringe
  3. filtrationfilter
  4. wash(washed with small amount of THF)
  5. customThe filtrate was purified by preparative HPLC (
  6. washeluting with a gradient of 25-50% ACN (containing 0.035% TFA) in water (containing 0.05% TFA)
  7. additionThe fractions containing the desired product
  8. customwere evaporated under reduced pressure
  9. additionThen NaHCO3 aqueous solution was added (in order
  10. extractionextracted with EtOAc (THF
  11. additionwas added
  12. dissolutionto dissolve the precipitate)
  13. dry with materialThe combined organic phases were dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-90e1d9b3ff1445fe90cf3c1c82378932
出典データセット
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08163755B2

反応ノート

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