m-Chloroperbenzoic acid → 5-[7-(3,3-difluorocyclobutyl)-2-(methylsulfinyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine

HRID 1775473Notes

Reaction equation

[F:1][C:2]1([F:24])[CH2:5][CH:4]([N:6]2[C:10]3[N:11]=[C:12]([S:22][CH3:23])[N:13]=[C:14]([C:15]4[CH:16]=[N:17][C:18]([NH2:21])=[N:19][CH:20]=4)[C:9]=3[CH2:8][CH2:7]2)[CH2:3]1.ClC1C=CC=C(C(OO)=[O:33])C=1>C(Cl)Cl>[F:24][C:2]1([F:1])[CH2:3][CH:4]([N:6]2[C:10]3[N:11]=[C:12]([S:22]([CH3:23])=[O:33])[N:13]=[C:14]([C:15]4[CH:20]=[N:19][C:18]([NH2:21])=[N:17][CH:16]=4)[C:9]=3[CH2:8][CH2:7]2)[CH2:5]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of crude 5-[7-(3,3-difluorocyclobutyl)-2-(methylsulfanyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine (˜80% purity) (768 mg, 2.63 mmol) in DCM (87 mL) at 0° C. was added m-chloroperbenzoic acid (844 mg, 3.42 mmol, 70% purity) in three portions over 1 min. The reaction mixture was stirred at 0° C. for 15 min, whereupon it was diluted with DCM and washed with saturated aqueous NaHCO3 and water. The organic layer was concentrated and purified via HPLC reversed phase column (0-50% of gradient A to B over 25 min; A: water with 0.1% acetic acid, B: acetonitrile with 0.1% acetic acid) to afford the title compound (251 mg, 26%). 1H NMR (400 MHz, DMSO-d6) δ 8.80 (s, 2 H), 7.19 (s, 2 H), 4.61-4.48 (m, 1 H), 3.83 (t, J=8.4 Hz, 2 H), 3.38-3.31 (m, 2 H), 3.14-2.98 (m, 2 H), 2.97-2.85 (m, 2 H), 2.83 (s, 3 H). m/z (APCI+) for C15H16F2N6OS 367.1 (M+H)+.

Workup

washwashed with saturated aqueous NaHCO3 and water
concentrationThe organic layer was concentrated
custompurified via HPLC
customover 25 min

Sources & evidence

ORD record: ord-b7b26622fffc4621803a7e8927a1d375
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260439B2

Reaction notes

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