1,2-Dimethoxyethane → 4-{4-[6-Amino-5-(3-methylbenzo[b]thiophen-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1926332

反応式

HRID 1926332 の反応式
COCCOC.CC1(C)C(C)(C)OB([C:15]2[S:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[C:16]=2[CH3:24])O1.[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([N:39]2[CH:43]=[C:42]([C:44]3[CH:45]=[N:46][C:47]([NH2:51])=[C:48](Br)[CH:49]=3)[CH:41]=[N:40]2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].C(=O)([O-])[O-].[K+].[K+]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.C(Cl)Cl.O>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([N:39]2[CH:43]=[C:42]([C:44]3[CH:45]=[N:46][C:47]([NH2:51])=[C:48]([C:15]4[S:19][C:18]5[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=5[C:16]=4[CH3:24])[CH:49]=3)[CH:41]=[N:40]2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

参加物

8

反応物 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 591331964,4,5,5-Tetramethyl-2-(3-methyl-1-benzothiophen-2-yl)-1,3,2-dioxaborolaneHCID 67366272tert-butyl 4-(4-(6-amino-5-bromopyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

生成物 1

HCID 675210534-{4-[6-Amino-5-(3-methylbenzo[b]thiophen-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 18456801dichloropalladium DCM触媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

To the DME solution of 4,4,5,5-tetramethyl-2-(3-methylbenzo[b]thiophen-2-yl)-[1,3,2]dioxaborolane (2.3 mL, 0.50 mmol, 2 eq.) from the previous step were added 4-[4-(6-amino-5-bromopyridin-3-yl)-pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl ester (BB3) (120 mg, 0.29 mmol, 1 eq.), potassium carbonate (104 mg, 0.75 mmol, 3 eq.), water (0.5 mL), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium DCM (10 mg, 0.01 mmol, 0.05 eq.). The mixture was evacuated and filled with nitrogen (3×) and heated in a microwave reactor to 100° C. for 30 min. The crude was passed through Thiol-SPE to remove Pd. The clear solution was purified with the MDPS. 1H NMR (400 MHz, CD3OD): δ=1.47 (s, 9H), 1.87-2.00 (m, 2H), 2.09 (d, J=10.4 Hz, 2H). 2.31 (s, 3H), 2.95 (br. s., 2H), 3.35 (s, 2H), 4.22 (d, J=13.4 Hz, 2H), 4.37 (tt, J=11.6, 4.1 Hz, 1H), 7.36-7.47 (m, 2H), 7.75-7.82 (m, 3H), 7.87 (d, J=7.6 Hz, 1H), 8.05 (s, 1H), 8.25 (d, J=1.8 Hz, 1H). MS (ES+): m/z=490.37 (100) [MH+]. HPLC: tR=0.93 min (UPLC-ACQUITY, Analytical).

後処理

  1. customThe mixture was evacuated
  2. additionfilled with nitrogen (3×)
  3. customto remove Pd
  4. customThe clear solution was purified with the MDPS

出典と根拠

ORDレコード
ord-cf7442ce83414a86b14b111e19a9f2cb
出典データセット
uspto-grants-2012_05
特許番号
US08178668B2

関連ノート

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