Isopropyl iodide → 3-(1,3-Benzoxazol-2-yl)-5-[1-(1-isopropyl-4-piperidyl)pyrazol-4-yl]pyridin-2-amine

HRID 908371Notes

Reaction equation

I[CH:2]([CH3:4])[CH3:3].[O:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[C:14]1[C:15]([NH2:31])=[N:16][CH:17]=[C:18]([C:20]2[CH:21]=[N:22][N:23]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[CH:24]=2)[CH:19]=1.C(N(CC)CC)C>CC(N(C)C)=O>[O:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[C:14]1[C:15]([NH2:31])=[N:16][CH:17]=[C:18]([C:20]2[CH:21]=[N:22][N:23]([CH:25]3[CH2:26][CH2:27][N:28]([CH:2]([CH3:4])[CH3:3])[CH2:29][CH2:30]3)[CH:24]=2)[CH:19]=1

Participants

Conditions

Temperature: 50 °C

Procedure

2-Iodopropane (0.029 ml) was added in one portion to 3-(1,3-benzoxazol-2-yl)-5-[1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (0.100 g) and triethylamine (0.05 8 ml) in DMA (3 ml) and the resulting solution was stirred for 30 minutes. A further portion of 2-iodopropane (0.029 ml) was added, the temperature was increased to 50° C. and the reaction mixture was stirred for a further 90 minutes. A third portion of 2-iodopropane (0.029 ml) was added, and then triethylamine (0.058 ml) was added and the reaction heated at 50° C. for a further hour. The reaction mixture was then evaporated to dryness and redissolved in DMSO (3.6 ml) and the crude product was purified by preparative X bridge HPLC (C18 OBD column, 5μ silica, 21 mm diameter, 100 mm length using decreasingly polar mixtures of water containing 1% ammonia and MeCN as eluents). There was thus obtained 3-(1,3-benzoxazol-2-yl)-5-[1-(1-isopropyl-4-piperidyl)pyrazol-4-yl]pyridin-2-amine (0.065 g); Mass Spectrum: M+H+ 403.17; RT 2.49 min; NMR Spectrum: (DMSOd6) 8.53 (1H, d), 8.44 (1H, d), 8.32 (1H, s), 7.90 (1H, s), 7.82-7.86 (1H, m), 7.77-7.81 (1H, m), 7.62 (2H, s), 7.41-7.49 (2H, m), 4.05-4.16 (1H, m), 2.91 (2H, d), 2.77 (1H, quintet), 2.29 (2H, t), 2.02-2.11 (2H, m), 1.94 (2H, qd), 1.01 (6H, d).

Workup

stirringthe reaction mixture was stirred for a further 90 minutes
temperaturethe reaction heated at 50° C. for a further hour
customThe reaction mixture was then evaporated to dryness
dissolutionredissolved in DMSO (3.6 ml)
customthe crude product was purified by preparative X bridge HPLC (C18 OBD column, 5μ silica, 21 mm diameter, 100 mm length
customRT 2.49 min

Sources & evidence

ORD record: ord-cf93237edb06422592b5610964713579
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08017611B2

Reaction notes

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