Sodium Carbonate → 4-[4-Morpholin-4-yl-6-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-1,3,5-triazin-2-yl]aniline

HRID 707080Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[CH:19]3[CH2:20][CH2:21][CH:15]2[CH2:16][O:17][CH2:18]3)[N:3]=1.[NH2:22][C:23]1[CH:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[N:8]1([C:6]2[N:5]=[C:4]([N:14]3[CH:19]4[CH2:20][CH2:21][CH:15]3[CH2:16][O:17][CH2:18]4)[N:3]=[C:2]([C:26]3[CH:27]=[CH:28][C:23]([NH2:22])=[CH:24][CH:25]=3)[N:7]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Participants

Conditions

Temperature: 130 °C

Procedure

To a 10 mL vial were added 8-(4-chloro-6-morpholino-1,3,5-triazin-2-yl)-3-oxa-8-azabicyclo[3,2,1]octane (311 mg, 1.0 mmol), 4-aminophenylboronic acid pinacol ester (328 mg, 1.5 mmol), Pd(PPh3)4 (58 mg, 5 mol %), 1,2-dimethoxyethane (DME, 2.5 mL) and 2M Na2CO3 aqueous solution (1.5 mL). The resulting mixture was heated at 130° C. for 30 min in microwave oven. The reaction mixture was cooled to room temperature. The aqueous phase was extracted with EtOAc, and the combined organic phases were dried over (MgSO4). The solvent was removed under reduced pressure and the residue was subjected to HPLC separation to give the title compound as off-white solid (280 mg, 76% yield). MS (ESI) m/z 369.2.

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionThe aqueous phase was extracted with EtOAc
dry with materialthe combined organic phases were dried over (MgSO4)
customThe solvent was removed under reduced pressure
customthe residue was subjected to HPLC separation

Sources & evidence

ORD record: ord-9f670886d0074a3e98c598218d024e79
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174963B2

Reaction notes

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