Morpholine → HCID 86706970, compound

HRID 1750299Notes

Reaction equation

Cl[C:2]1[C:3]2[C:10]([C:11]3([OH:17])[CH2:16][CH2:15][CH2:14][O:13][CH2:12]3)=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(N(CC)C(C)C)(C)C>C(O)CCC>[N:18]1([C:2]2[C:3]3[C:10]([C:11]4([OH:17])[CH2:16][CH2:15][CH2:14][O:13][CH2:12]4)=[CH:9][NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 3-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl)tetrahydro-2H-pyran-3-ol (C32) (200 mg, 0.79 mmol) and morpholine (134 mg, 1.54 mol) in n-butanol (10 mL) was added N,N-diisopropylethylamine (305 mg, 2.36 mol), and the reaction mixture was heated at 70° C. for 2 hours. After concentration in vacuo, preparative reversed phase high-performance liquid chromatography (Column: Phenomenex Gemini C18, 8 μm; Mobile phase A: aqueous ammonia, pH 10; Mobile phase B: acetonitrile; Gradient: 9% to 29% B) provided the product as a white solid. Yield: 180 mg, 0.59 mmol, 75%. LCMS m/z 305.1 [M+H+]. 1H NMR (400 MHz, CDCl3+D2O) δ 8.73 (s, 1H), 7.52 (s, 1H), 3.92-4.03 (m, 4H), 3.74-3.88 (m, 4H), 3.32-3.40 (m, 2H), 3.15-3.24 (m, 2H), 2.07-2.16 (m, 1H), 1.88-2.06 (m, 2H), 1.57-1.68 (m, 1H).

Workup

concentrationAfter concentration in vacuo, preparative reversed phase high-performance liquid chromatography (Column: Phenomenex Gemini C18, 8 μm; Mobile phase A: aqueous ammonia, pH 10; Mobile phase B: acetonitrile; Gradient: 9% to 29% B)

Sources & evidence

ORD record: ord-6fed540b97b045c6aac535f956e579d8
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156845B2

Reaction notes

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