Isopropanol → HCID 118208486、化合物

HRID 595289ノート

反応式

HRID 595289 の反応式
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]

参加物

9

反応物 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

生成物 1

HCID 118208486HCID 118208486、化合物

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-bb85f59eb99c4fa38775d3b2796b9563
出典データセット
uspto-grants-2016_01
特許番号
US09242984B2

反応ノート

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