Diisopropylethylamine → 2-(4-{2-[4-(Pyrimidin-2-yloxy)piperidin-1-yl]ethoxy}phenoxy)[1,3]thiazolo[4,5-b]pyridine

HRID 547353Notes

Reaction equation

Br[CH2:2][CH2:3][O:4][C:5]1[CH:20]=[CH:19][C:8]([O:9][C:10]2[S:11][C:12]3[C:13]([N:18]=2)=[N:14][CH:15]=[CH:16][CH:17]=3)=[CH:7][CH:6]=1.[NH:21]1[CH2:26][CH2:25][CH:24]([O:27][C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)[CH2:23][CH2:22]1.C(N(CC)C(C)C)(C)C>CC#N>[N:29]1[CH:30]=[CH:31][CH:32]=[N:33][C:28]=1[O:27][CH:24]1[CH2:25][CH2:26][N:21]([CH2:2][CH2:3][O:4][C:5]2[CH:20]=[CH:19][C:8]([O:9][C:10]3[S:11][C:12]4[C:13]([N:18]=3)=[N:14][CH:15]=[CH:16][CH:17]=4)=[CH:7][CH:6]=2)[CH2:22][CH2:23]1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 2-[4-(2-bromoethoxy)phenoxy][1,3]thiazolo[4,5-b]pyridine (131 mg, 0.37 mmol) and 2-(piperidin-4-yloxy)-pyrimidine (80 mg, 0.45 mmol, 1.2 equiv.) in CH3CN (1.9 mL) was added N,N-diisopropylethylamine (97 μL, 0.56 mmol, 1.5 equiv.). The resulting solution was allowed to stir at 70° C. for 18 h. The solution was then cooled to rt, filtered and purified using preparative reverse phase HPLC to afford the desired product as a yellow-brown solid (64 mg, 38%). 1H NMR (600 MHz, CDCl3): 8.58-8.54 (m, 1H), 8.52-8.48 (m, 2H), 8.01-7.96 (m, 1H), 7.34-7.30 (m, 2H), 7.18 (dd, J=6.7, 4.8, 1H), 6.96 (d, J=8.1, 2H), 6.92-6.87 (m, 1H), 5.14-5.04 (m, 1H), 4.14 (t, J=5.6, 2H), 2.96-2.88 (m, 2H), 2.86 (t, J=5.5, 2H), 2.56-2.46 (m, 2H), 2.16-2.04 (m, 2H), 2.01-1.90 (m, 2H). MS (ESI): mass calcd. for C23H23N5O3S, 449.15; m/z found, 450.1 [M+H]+.

Workup

temperatureThe solution was then cooled to rt
filtrationfiltered
custompurified

Sources & evidence

ORD record: ord-1b70da7fae9844d5b1a65290c6946f55
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07939527B2

Reaction notes

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