Tetrabutylammonium Fluoride → HCID 71715823, compound

HRID 538926Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]2[CH:17]=[C:16]([N:18]3[C@@H:22]4[CH2:23][CH2:24][C@@H:25]([O:26][Si](C(C)(C)C)(C)C)[C@@H:21]4[O:20][C:19]3=[O:34])[N:15]=[C:14]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[N:13]=2)=[CH:4][N:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]2[CH:17]=[C:16]([N:18]3[C@@H:22]4[CH2:23][CH2:24][C@@H:25]([OH:26])[C@@H:21]4[O:20][C:19]3=[O:34])[N:15]=[C:14]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[N:13]=2)=[CH:4][N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (3aR*,6R*,6aR*)-3-(2′-amino-2-morpholino-4′-(trifluoromethyl)-[4,5′-bipyrimidin]-6-yl)-6-((tert-butyldimethylsilyl)oxy)hexahydro-2H-cyclopenta[d]oxazol-2-one (810 mg, 1.253 mmol) in THF (12 mL), was added dropwise 1M TBAF in THF (1.0 mL, 1.0 mmol) at 0° C. The reaction mixture was stirred for 30 min at 0° C. and 2 h at RT before evaporation. The residue was purified by flash chromatography (hexane-THF 60:40→0:100). The residue was triturated in Et2O, filtered and dried. The residue was purified by preparative HPLC (Waters Sun Fire C18, 30×100 mm, 5 um; 0.1% TFA-water/acetonitrile; gradient acetonitrile 5-100% in 20 min) to afford the title compound (430 mg, 72%); tR=0.93 min (UPLC 1), tR=0.81 min (LC-MS 3); ESI-MS: 468 [M+H]+ (LC-MS 3).

Workup

customThe residue was purified by flash chromatography (hexane-THF 60:40→0:100)
customThe residue was triturated in Et2O
filtrationfiltered
customdried
customThe residue was purified by preparative HPLC (Waters Sun Fire C18, 30×100 mm, 5 um; 0.1% TFA-water/acetonitrile; gradient acetonitrile 5-100% in 20 min)

Sources & evidence

ORD record: ord-0c5b021de8e54cb7b46b851df04015af
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08865894B2

Reaction notes

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