Isopropanol → HCID 118208486, 화합물

HRID 595289

반응식

HRID 595289 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)O1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)NC(OC(C)C)=O.[CH:48](O)([CH3:50])[CH3:49].Br[C:53]1[CH:54]=[C:55]([NH:60][C:61]2[N:66]=[C:65]([C:67]([F:70])([F:69])[F:68])[CH:64]=[CH:63][N:62]=2)[CH:56]=[C:57]([CH3:59])[CH:58]=1.C(=O)([O-])[O-].[Na+].[Na+]>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:48]([N:12]1[CH:13]=[C:9]([C:53]2[CH:54]=[C:55]([NH:60][C:61]3[N:66]=[C:65]([C:67]([F:69])([F:70])[F:68])[CH:64]=[CH:63][N:62]=3)[CH:56]=[C:57]([CH3:59])[CH:58]=2)[CH:10]=[N:11]1)([CH3:50])[CH3:49]

참가 물질

9

반응물 6

HCID 3776IsopropanolHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 88220Diisopropyl bicarbamateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58456396N-(3-bromo-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

생성물 1

HCID 118208486HCID 118208486, 화합물

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8028Tetrahydrofuran용매2회

실험 절차

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.02 g, 0.10 mmol), polystyrene supported-triphenylphosphine (0.12 g, 0.24 mmol, 1.92 mmol/g), diisopropyl hydrazine-1,2-dicarboxylate (0.04 g, 0.19 mmol), and isopropanol (0.01 g, 0.21 mmol) were suspended in THF (1.0 mL). The reaction was allowed to shake at ambient temperature for 48 hours. The reaction mixture was filtered, the eluent was collected and concentrated under reduced pressure. Pd(dppf)Cl2 (0.011 g, 0.015 mmol), N-(3-bromo-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine (0.03 g, 0.08 mmol), sodium carbonate (0.10 mL, 0.20 mmol, 2 M) suspended in THF (1.0 mL) were added. The vial was capped and irradiated in a microwave for 15 minutes at 110° C. Silica supported-DMT (0.055 g, 0.05 mmol, 0.94 mmol/g) was added, the vial was sealed and allowed to stir for 4 hours. The reaction mixture was passed through a syringe filter, the eluent was collected and concentrated under reduced pressure. The residue was purified by reverse phase HPLC (0 to 95% ACN/water with 0.1% TFA modifier) to afford N-(3-(1-isopropyl-1H-pyrazol-4-yl)-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine. MS ESI calc'd for C18H19F3N5 [M+H]+ 362. found 362. 1H NMR (500 MHz, DMSO-d6) δ 10.10 (s, 1H), 8.80 (d, J=4.8, 1H), 8.08 (s, 1H), 7.84 (s, 1H), 7.71 (s, 1H), 7.29 (s, 1H), 7.23 (d, J=4.9, 1H), 7.07 (s, 1H), 4.49 (dt, J=6.6, 13.3, 1H), 2.28 (s, 3H), 1.43 (d, J=6.7, 6H).

후처리

  1. filtrationThe reaction mixture was filtered
  2. customthe eluent was collected
  3. concentrationconcentrated under reduced pressure
  4. additionwere added
  5. customThe vial was capped
  6. customirradiated in a microwave for 15 minutes at 110° C
  7. additionSilica supported-DMT (0.055 g, 0.05 mmol, 0.94 mmol/g) was added
  8. customthe vial was sealed
  9. customThe reaction mixture was passed through a syringe
  10. filtrationfilter
  11. customthe eluent was collected
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by reverse phase HPLC (0 to 95% ACN/water with 0.1% TFA modifier)

출처 및 근거

ORD 기록
ord-bb85f59eb99c4fa38775d3b2796b9563
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242984B2

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