Potassium Carbonate → HCID 86302751, compound

HRID 1778181Notes

Reaction equation

CS([C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[N:13][C:14]([NH2:17])=[N:15][CH:16]=2)[CH:8]=[C:7]([N:18]2[CH2:23][C@@H:22]3[CH2:24][C@H:19]2[CH2:20][O:21]3)[N:6]=1)(=O)=O.Cl.[NH:26]1[CH2:29][CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O>[N:26]1([C:5]2[N:10]=[C:9]([C:11]3[CH:12]=[N:13][C:14]([NH2:17])=[N:15][CH:16]=3)[CH:8]=[C:7]([N:18]3[CH2:23][C@@H:22]4[CH2:24][C@H:19]3[CH2:20][O:21]4)[N:6]=2)[CH2:29][CH2:28][CH2:27]1

Participants

Conditions

Temperature: 130 °C

Procedure

5-[2-methylsulfonyl-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine (30.0 mg, 0.861 mmol), azetidine hydrochloride (24.7 mg, 0.258 mmol), potassium carbonate (71.4 mg, 0.517 mmol), and 1-methyl-2-pyrrolidinone (0.861 mL) were combined in a reaction flask and heated to 130° C. for 16 hrs. The reaction was filtered and purified by reverse phase column chromatography using a gradient of 20% to 60% acetonitrile in 0.1% ammonium hydroxide in water. The combined fractions containing product were concentrated under reduced pressure to provide 2-(azetidin-1-yl)-6-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-[4,5′-bipyrimidin]-2′-amine 1H NMR (400 MHz, DMSO-d6) δ 8.87 (s, 2H), 6.97 (s, 2H), 4.95 (s, 1H), 4.66 (s, 1H), 3.99 (t, J=7.5 Hz, 4H), 3.77 (dd, J=7.3, 1.5 Hz, 1H), 3.64 (d, J=7.3 Hz, 1H), 3.43 (dd, J=10.5, 1.5 Hz, 1H), 3.40-3.32 (m, 1H), 3.17 (s, 1H), 2.24 (p, J=7.5 Hz, 2H), 1.85 (s, 2H).

Workup

filtrationThe reaction was filtered
custompurified by reverse phase column chromatography
additionThe combined fractions containing product
concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record: ord-f0ea5ca757bb4ac397289f423d71c7c9
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266862B2

Reaction notes

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