Cesium carbonate → HCID 67521074、化合物

HRID 1926250ノート

反応式

HRID 1926250 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23](B4OC(C)(C)C(C)(C)O4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:35][C:36]1[CH:45]=[CH:44][C:43]([F:46])=[C:42]2[C:37]=1[CH:38]=[C:39](OS(C(F)(F)F)(=O)=O)[N:40]=[CH:41]2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23]([C:39]4[N:40]=[CH:41][C:42]5[C:37]([CH:38]=4)=[C:36]([Br:35])[CH:45]=[CH:44][C:43]=5[F:46])[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 534879604-[4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-3-yl]pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl esterHCID 86633137Trifluoromethanesulfonic acid 5-bromo-8-fluoroisoquinolin-3-yl ester

生成物 1

HCID 67521074HCID 67521074、化合物

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a solution of 4-{4-[6-amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB3) (370 mg, 0.67 mmol), trifluoromethanesulfonic acid 5-bromo-8-fluoroisoquinolin-3-yl ester (250 mg, 0.67 mmol), and Pd(PPh3)4 (40 mg, 0.03 mmol) in 1,4-dioxane (8.0 mL) in a sealable microwave tube was added a solution of Cs2CO3 (440 mg, 1.3 mmol) in H2O (2 mL). The tube was sealed, evacuated and refilled with nitrogen (3×), and heated in the microwave reactor to 100° C. for 30 minutes. The reaction mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel, eluting with 5% 7M NH3 in MeOH and DCM. One obtained the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3): δ=1.24-1.35 (m, 4H), 1.49 (s, 9H), 1.93-2.06 (m, 2H), 2.19 (d, J=2.3 Hz, 1H), 2.86-2.96 (m, 1H), 6.55 (br. s., 2H), 7.17 (dd, J=9.4, 8.3 Hz, 1H), 7.68 (s, 1H), 7.80 (s, 1H), 7.95 (dd, J=8.3, 4.8 Hz, 1H), 8.00 (d, J=2.3 Hz, 1H), 8.31 (s, 1H), 8.32 (d, J=2.3 Hz, 1H), 9.57 (s, 1H). MS (ES+): m/z=566.87/567.69 [MH+]. HPLC: tR=3.08 min (ZQ2, polar—5 min).

後処理

  1. customThe tube was sealed
  2. customevacuated
  3. additionrefilled with nitrogen (3×)
  4. additionThe reaction mixture was diluted with EtOAc
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography on silica gel
  10. washeluting with 5% 7M NH3 in MeOH and DCM

出典と根拠

ORDレコード
ord-c00ddeb03e11478eb6e92b377d9ab922
出典データセット
uspto-grants-2012_05
特許番号
US08178668B2

反応ノート

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