tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate → HCID 66760893, compound

HRID 389452Notes

Reaction equation

HRID 389452 reaction equation
[Cl:1][C:2]1[O:12][C:5]2=[C:6]([NH2:11])[N:7]=[CH:8][C:9](I)=[C:4]2[C:3]=1[Cl:13].C(OC([N:21]1[CH2:26][CH2:25][CH:24]([N:27]2[CH:31]=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:29]=[N:28]2)[CH2:23][CH2:22]1)=O)(C)(C)C>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>[Cl:1][C:2]1[O:12][C:5]2=[C:6]([NH2:11])[N:7]=[CH:8][C:9]([C:30]3[CH:29]=[N:28][N:27]([CH:24]4[CH2:25][CH2:26][NH:21][CH2:22][CH2:23]4)[CH:31]=3)=[C:4]2[C:3]=1[Cl:13]

Participants

6

Reactant 2

HCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 667594452,3-Dichloro-4-iodofuro[2,3-c]pyridin-7-amine

Product 1

HCID 66760893HCID 66760893, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2,3-dichloro-4-iodo-furo[2,3-c]pyridin-7-ylamine (300.0 mg, 0.9121 mmol), 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (516 mg, 1.37 mmol) and Pd(PPh3)4 (50 mg, 0.04 mmol) in 1,4-dioxane (20 mL) and H2O (2 mL) was degassed and refilled with argon (3×). The reaction was heated at 100° C. for 20 h using a Biotage Initiator microwave reactor. The reaction was concentrated in vacuo to give a solid which was purified by flash chromatography (30 to 60% EtOAc:hexanes), which afforded the desired intermediate. 1H NMR (400 MHz, CDCl3): δ 7.85 (s, 1H), 7.65 (s, 1H), 7.57 (s, 1H), 4.80 (br s, 2H), 4.32 (m, 3H), 2.99 (m, 2H), 2.18 (m, 2H), 1.97 (m, 2H), 1.47 (s, 9H); MS (ESI): 452.00 [M+H]+; HPLC tR=3.14 min.

Workup

  1. customwas degassed
  2. additionrefilled with argon (3×)
  3. concentrationThe reaction was concentrated in vacuo
  4. customto give a solid which
  5. customwas purified by flash chromatography (30 to 60% EtOAc:hexanes), which

Sources & evidence

ORD record
ord-b2eddd7c047e40689122c6c65d277c0c
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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