Diisopropylethylamine → HCID 86677836, compound

HRID 1499915Notes

Reaction equation

FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([CH:26]([C:28]3[CH:35]=[C:34]([CH3:36])[C:31]([C:32]#[N:33])=[C:30]([CH:37]4[CH2:40][NH:39][CH2:38]4)[C:29]=3[O:41][CH3:42])[CH3:27])[N:23]=[C:24]([CH3:25])[C:17]=12.CCN(C(C)C)C(C)C.[CH3:52][C@H:53]1[CH2:55][O:54]1>C(O)C>[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([CH:26]([C:28]3[CH:35]=[C:34]([CH3:36])[C:31]([C:32]#[N:33])=[C:30]([CH:37]4[CH2:40][N:39]([CH2:52][C@@H:53]([OH:54])[CH3:55])[CH2:38]4)[C:29]=3[O:41][CH3:42])[CH3:27])[N:23]=[C:24]([CH3:25])[C:17]=12

Participants

Conditions

Temperature: 90 °C

Procedure

The 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-azetidin-3-yl-3-methoxy-6-methylbenzonitrile bis(trifluoroacetate) (0.074 g, 0.10 mmol) was dissolved in ethanol (3.0 mL) and DIPEA (0.071 mL, 0.41 mmol) and the (S)-(−)-methyloxirane (0.0071 g, 0.12 mmol) was added. The reaction was heated in a sealed tube to 90° C. and monitored by LC/MS. After heating for 6 hrs the reaction was purified without workup by prep HPLC on a C-18 column eluting water:acetonitrile gradient buffered pH 10 to give the title compound as a white amorphous solid (0.018 g, 40%). The product was isolated as a single enantiomer. LCMS calculated for C23H30N7O2(M+H)+: m/z=436.2; found: 436.3. 1H NMR (300 MHz, DMSO-d6) δ 8.09 (s, 1H), 7.21 (s, 1H), 6.22 (q, J=7.1 Hz, 1H), 4.34 (d, J=4.5 Hz, 1H), 4.09-3.83 (m, 3H), 3.60 (s, 3H), 3.58-3.51 (m, 1H), 3.12-2.95 (m, 2H), 2.55 (s, 3H), 2.33 (s, 3H), 2.27 (d, J=5.9 Hz, 2H), 1.71 (d, J=7.1 Hz, 3H), 1.00 (d, J=6.2 Hz, 3H).

Workup

temperatureAfter heating for 6 hrs the reaction
customwas purified without workup by prep HPLC on a C-18 column
washeluting water

Sources & evidence

ORD record: ord-60c7b34c81964b5e865eaf18c06c8367
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199982B2

Reaction notes

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