Sodium Bicarbonate → HCID 58169810, 화합물

HRID 1696035노트

반응식

HRID 1696035 반응식
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([OH:16])([CH3:15])[CH3:14])[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.[CH3:23][NH:24][C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][CH:29]=1)=[O:26].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]>[OH:16][C:13]([CH3:15])([CH3:14])[CH2:12][N:8]1[C:7](=[O:17])[C:6]2([CH3:22])[CH2:18][O:19][CH2:20][CH2:21][N:5]2[C:4]2[N:3]=[C:2]([C:31]3[CH:30]=[CH:29][C:28]([NH:27][C:25]([NH:24][CH3:23])=[O:26])=[CH:33][CH:32]=3)[N:11]=[CH:10][C:9]1=2

참가 물질

7

반응물 3

HCID 516892Sodium BicarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 86651593HCID 86651593, 화합물

생성물 1

HCID 58169810HCID 58169810, 화합물수율 18.5%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8028Tetrahydrofuran용매HCID 312751,4-Dioxane용매

실험 절차

A mixture of 2-chloro-5-(2-hydroxy-2-methylpropyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (84.9 mg, 0.260 mmol), 1-methyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenyl]-urea (143 mg, 0.520 mmol), saturated aqueous NaHCO3 (1 ml) and PdCl2(dppf) (17.0 mg, 0.021 mmol) in 1,4-dioxane (2 ml) was irradiated in the 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 MeOH). The filtrate was purified by preparative HPLC (eluting with a gradient of 20-20% 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. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo to afford a crude solid. The solid was triturated with hexane/ethyl acetate (3:1), collected by filtration, rinsed with hexane/ethyl acetate (3:1) and dried to afford the title compound (21.1 mg, 0.048 mmol, 18.4% yield) as a pale beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (s, 3 H) 1.15 (s, 3 H) 1.35 (s, 3 H) 2.66 (d, J=4.55 Hz, 3 H) 3.19-3.33 (m, 1 H) 3.52-3.80 (m, 3 H) 3.94-4.11 (m, 3 H) 4.12-4.22 (m, 1 H) 4.67 (s, 1 H) 6.00-6.10 (m, 1 H) 7.48 (d, J=8.84 Hz, 2 H) 8.17 (d, J=8.84 Hz, 2 H) 8.58 (s, 1 H) 8.68 (s, 1 H). MS [M+H] found 441.

후처리

  1. customwas irradiated in the 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 MeOH)
  5. customThe filtrate was purified by preparative HPLC (
  6. washeluting with a gradient of 20-20% 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
  11. dry with materialThe combined organic phases were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto afford a crude solid
  15. customThe solid was triturated with hexane/ethyl acetate (3:1)
  16. filtrationcollected by filtration
  17. washrinsed with hexane/ethyl acetate (3:1)
  18. customdried

출처 및 근거

ORD 기록
ord-3f6eaadc0fb4429baa2fc37507766cf2
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163755B2

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