Potassium Iodide → 1-Isopropyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine

HRID 389454Notes

Reaction equation

Cl.[CH3:2][C:3]1([CH3:21])[C:7]([CH3:9])([CH3:8])[O:6][B:5]([C:10]2[CH:11]=[N:12][N:13]([CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[CH:14]=2)[O:4]1.BrCCO[Si]([C:29](C)([CH3:31])[CH3:30])(C)C.CCN(C(C)C)C(C)C.[I-].[K+]>CN(C=O)C>[CH3:30][CH:29]([N:18]1[CH2:19][CH2:20][CH:15]([N:13]2[CH:14]=[C:10]([B:5]3[O:6][C:7]([CH3:8])([CH3:9])[C:3]([CH3:21])([CH3:2])[O:4]3)[CH:11]=[N:12]2)[CH2:16][CH2:17]1)[CH3:31]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine hydrochloride (500 mg, 1.59 mmol) in DMF (15.0 mL) was charged with (2-bromoethoxy)-tert-butyldimethylsilane (0.376 mL, 1.75 mmol), DIPEA (0.694 mL, 3.99 mmol) and potassium iodide (26 mg, 0.16 mmol) and was heated at 50° C. for 16 h. The DMF was then concentrated in vacuo. The product was purified by flash chromatography (0 to 15% MeOH:EtOAc) to afford the title compound. 1H NMR (400 MHz, CD3OD): δ 7.90 (s, 1H), 7.69 (s, 1H), 4.31 (td, J=7.71, 15.41 Hz, 1H), 3.88 (t, J=5.68 Hz, 2H), 3.28 (br s, 2H), 3.00 (s, 3H), 2.86 (s, 3H), 2.76-2.84 (m, 2H), 2.51-2.67 (m, 2H), 2.10-2.19 (m, 4H), 1.31 (s, 12H), 0.91-0.94 (m, 9H); MS (ESI): 436.28 [M+H]+; HPLC tR=1.26 min (TOF polar—3 min).

Workup

concentrationThe DMF was then concentrated in vacuo
customThe product was purified by flash chromatography (0 to 15% MeOH:EtOAc)

Sources & evidence

ORD record: ord-50c760042e4e4005a9bb7ab7327cd60d
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08378104B2

Reaction notes

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