Benzeneethanamine, alpha-methyl-, phosphate (1:1) → (S)-2'-(1H-imidazol-2-yl)-7'-(neopentyloxy)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

HRID 335762

Reaction equation

[CH2:1]([O:6][C:7]1[CH:20]=[CH:19][C:18]2[O:17][C:16]3[C:11](=[CH:12][C:13](B4OC(C)(C)C(C)(C)O4)=[CH:14][CH:15]=3)[C@@:10]3([CH2:33][O:32][C:31]([NH2:34])=[N:30]3)[C:9]=2[CH:8]=1)[C:2]([CH3:5])([CH3:4])[CH3:3].Br[C:36]1[NH:37][CH:38]=[CH:39][N:40]=1.CC([O-])=O.[K+].CC(N)CC1C=CC=CC=1.OP(O)(O)=O>C(O)CCC.O.CO>[NH:37]1[CH:38]=[CH:39][N:40]=[C:36]1[C:13]1[CH:14]=[CH:15][C:16]2[O:17][C:18]3[C:9](=[CH:8][C:7]([O:6][CH2:1][C:2]([CH3:5])([CH3:4])[CH3:3])=[CH:20][CH:19]=3)[C@:10]3([CH2:33][O:32][C:31]([NH2:34])=[N:30]3)[C:11]=2[CH:12]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of (S)-2′-(neopentyloxy)-7′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (50 mg, 0.108 mmol) in BuOH (861 μL), 2-bromo-1H-imidazole (0.129 mmol), and KOAc (31.7 mg, 0.323 mmol) in Water (215 μL) was purged with Ar in a sealed tube. AmPhos (1.525 mg, 2.153 μmol) was added and the reaction was heated to 120° C. for 30 min in the microwave. The reaction was cooled to rt, diluted with MeOH (3 ml), loaded onto an AccuBOND II SCX cartridge, washed with MeOH (3 ml) and eluted with 2N NH3 in MeOH (6 ml) to give the crude product which was purified by reverse-phase preparative HPLC using a Gemini NX c!8 column (150*30 mm, 5 um), 0.1% TFA in CH3CN/H2O, gradient 0% to 70% over 10 min to provide (S)-2′-(1H-imidazol-2-yl)-7′-(neopentyloxy)-5H-spiro[oxazole-4,9′-xanthen]-2-amine.

Workup

temperatureThe reaction was cooled to rt
washwashed with MeOH (3 ml)
washeluted with 2N NH3 in MeOH (6 ml)
customto give the crude product which
customwas purified by reverse-phase preparative HPLC
customover 10 min

Sources & evidence

ORD record: ord-813580b86bc541abab42e4b658d2d333
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883782B2

Linked notes

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