Potassium Carbonate → tert-butyl 4-{4-[7-amino-2-(1-benzothiophen-7-yl)furo[2,3-c]pyridine-4-yl]-1H-pyrazol-1-yl}piperidine-1-carboxylate

HRID 389492Notes

Reaction equation

HRID 389492 reaction equation
[S:1]1[C:5]2[C:6](B(O)O)=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([N:26]2[CH:30]=[C:29]([C:31]3[CH:36]=[N:35][C:34]([NH2:37])=[C:33]4[O:38][C:39](Cl)=[CH:40][C:32]=34)[CH:28]=[N:27]2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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]>[NH2:37][C:34]1[N:35]=[CH:36][C:31]([C:29]2[CH:28]=[N:27][N:26]([CH:23]3[CH2:24][CH2:25][N:20]([C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])[CH2:21][CH2:22]3)[CH:30]=2)=[C:32]2[CH:40]=[C:39]([C:6]3[C:5]4[S:1][CH:2]=[CH:3][C:4]=4[CH:9]=[CH:8][CH:7]=3)[O:38][C:33]=12

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 166405281-Benzothien-7-ylboronic acidHCID 66760514HCID 66760514, compound

Product 1

HCID 66760630tert-butyl 4-{4-[7-amino-2-(1-benzothiophen-7-yl)furo[2,3-c]pyridine-4-yl]-1H-pyrazol-1-yl}piperidine-1-carboxylateYield 64%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 7-benzothiophene boronic acid, 4-[4-(7-amino-2-chloro-furo[2,3-c]pyridin-4-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (150 mg, 359 μmol), Pd(dppf)Cl2 (2.63 mg, 3.59 μmol), K2CO3, (74.4 mg, 538 μmol) in 1,4-dioxane (1.96 mL), and H2O (647 μL) was degassed and refilled with argon (3×). The reaction was heated in a microwave reactor at 100° C. for 70 min. The reaction was diluted with water, extracted with EtOAc (3×) and the combined extracts were dried over Na2SO4, then concentrated in vacuo to give a solid. The solid was purified by flash chromatography (60-100% EtOAc:hexanes) to afford 96 mg (64%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 8.03 (d, J=7.33 Hz, 1 H), 7.88-7.99 (m, 3 H), 7.75 (s, 1 H), 7.61 (d, J=5.31 Hz, 1 H), 7.56 (t, J=7.71 Hz, 1 H), 7.50 (d, J=5.56 Hz, 1 H), 7.44 (s, 1 H), 5.53 (br s, 2 H), 4.25-4.48 (m, 3 H), 2.90-3.01 (m, 2 H), 2.24 (d, J=15.16 Hz, 2 H), 1.97-2.11 (m, 2 H), 1.51 (s, 9 H); MS (ESI): 516.16 [M+H]+; HPLC tR=2.66 min.

Workup

  1. additionrefilled with argon (3×)
  2. extractionextracted with EtOAc (3×)
  3. dry with materialthe combined extracts were dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customto give a solid
  6. customThe solid was purified by flash chromatography (60-100% EtOAc:hexanes)

Sources & evidence

ORD record
ord-eb2566de318043d8b1ec206f0f8f2051
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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