Cesium carbonate → HCID 67520633、化合物

HRID 1926267ノート

反応式

HRID 1926267 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].[Cl:35][C:36]1[C:45]([F:46])=[CH:44][C:43]([F:47])=[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]([Cl:35])[C:45]([F:46])=[CH:44][C:43]=5[F:47])[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 86633145HCID 86633145、化合物

生成物 1

HCID 67520633HCID 67520633、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) (18.3 mg, 0.0391 mmol), trifluoromethanesulfonic acid 5-chloro-6,8-difluoroisoquinolin-3-yl ester (0.0326 mmol), and Pd(PPh3)4 (2.51 mg, 0.00215 mmol) in 1,4-dioxane (0.90 ml) in a sealable microwave tube was added a solution of Cs2CO3 (21.4 mg, 0.0651 mmol) in H2O (0.30 ml). The tube was sealed, evacuated and refilled with nitrogen (3×), and heated in the microwave reactor to 100° C. for 30 min. The reaction mixture was diluted with EtOAc (40 ml), washed with water (2×20 ml) and brine (20 ml), and dried over MgSO4. After concentration in vacuo, a brown oil was obtained. It was then purified by prep. TLC eluting with 4% MeOH/CH2Cl2 to give the title compound as a brown oil. 1H NMR (400 MHz, CDCl3): δ=1.49 (s, 9H), 1.94-2.05 (m, 2H), 2.16-2.24 (m, 2H), 2.87-2.98 (m, 2H), 4.24-4.38 (m, 3H), 6.45 (brs, 2H), 7.18 (t, J=9.6 Hz, 1H), 7.68 (d, J=0.8 Hz, 1H), 7.79 (d, J=0.8 Hz, 1H), 7.99 (d, J=2.4 Hz, 1H), 8.32 (d, J=2.4 Hz, 1H), 8.34 (m, 1H), 9.53 (d, J=1.2 Hz, 1H). MS(ES+): m/z=540.92/542.87 (100/86) [MH+]. HPLC: tR=3.15 min (ZQ3, 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 (40 ml)
  5. washwashed with water (2×20 ml) and brine (20 ml)
  6. dry with materialdried over MgSO4
  7. concentrationAfter concentration in vacuo
  8. customa brown oil was obtained
  9. customIt was then purified by prep

出典と根拠

ORDレコード
ord-ad2f580717584504855a96677ec22bfb
出典データセット
uspto-grants-2012_05
特許番号
US08178668B2

反応ノート

読み込み中…