[2-(2-Iodo-benzyl)-thiazolo[5,4-d]pyrimidin-7-yl]-(4-trifluoromethyl-phenyl)-amine → 2-[7-(4-Trifluoromethyl-phenylamino)-thiazolo[5,4-d]pyrimidin-2-ylmethyl]-benzonitrile

HRID 60206Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of [2-(2-iodo-benzyl)-thiazolo[5,4-d]pyrimidin-7-yl]-(4-trifluoromethyl-phenyl)-amine (0.20 g, 0.39 mmol) in anhydrous DMF (3.9 mL) was added copper cyanide (0.24, 2.73 mmol). The resulting suspension was heated to 100° C. in a sealed tube for 5 h. The reaction mixture was cooled to rt, diluted with H2O (20 mL) and extracted with EtOAc (2×10 mL). The organic layers were combined, washed with 10% aq. HCl (2×5 mL) and satd. aq. NaCl (2×5 mL), dried, filtered, concentrated and purified by FCC to provide the title compound as a colorless solid (0.15 g, 94%). MS (ESI): mass calcd. for C20H12F3N5S, 411.1; m/z found 412.1 [M+H]+. 1H NMR (CDCl3): 8.63 (s, 1H), 8.18 (s, 1H), 7.97 (d, J=8.5 Hz, 2H), 7.75-7.72 (d, J=8.5 Hz, 2H), 7.65-7.61 (m, 1H), 7.52-7.49 (m, 1H), 7.48-7.44 (m, 2H), 4.66 (s, 2H).

Workup

temperatureThe reaction mixture was cooled to rt
extractionextracted with EtOAc (2×10 mL)
washwashed with 10% aq. HCl (2×5 mL)
dry with materialaq. NaCl (2×5 mL), dried
filtrationfiltered
concentrationconcentrated
custompurified by FCC

Sources & evidence

ORD record: ord-32ed558cebe44002af62e9afd879d475
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440978B2

Reaction notes

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