Methanesulfonyl chloride → 2-{4-Chloro-6-[(3,3-difluorocyclobutyl)amino]-2-(methylsulfanyl)pyrimidin-5-yl}ethyl methanesulfonate

HRID 1775470Notes

Reaction equation

[Cl:1][C:2]1[C:7]([CH2:8][CH2:9][OH:10])=[C:6]([NH:11][CH:12]2[CH2:15][C:14]([F:17])([F:16])[CH2:13]2)[N:5]=[C:4]([S:18][CH3:19])[N:3]=1.[CH3:20][S:21](Cl)(=[O:23])=[O:22]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:20][S:21]([O:10][CH2:9][CH2:8][C:7]1[C:2]([Cl:1])=[N:3][C:4]([S:18][CH3:19])=[N:5][C:6]=1[NH:11][CH:12]1[CH2:13][C:14]([F:16])([F:17])[CH2:15]1)(=[O:23])=[O:22]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-{4-chloro-6-[(3,3-difluorocyclobutyl)amino]-2-(methylsulfanyl)pyrimidin-5-yl}ethanol (714 mg, 2.31 mmol) in DCM (38.5 mL) was added TEA (1.12 mL, 8.06 mmol), methanesulfonyl chloride (0.455 mL, 5.76 mmol) and DMAP (17 mg, 0.138 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h and at room temperature for 1 h. The reaction mixture was washed with water (3×), and the organic layer was dried (Na2SO4) and concentrated under reduced pressure to give 925 mg (>99%) of the title compound as a yellow solid. This material was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6) δ 7.67 (d, J=5.7 Hz, 1 H), 4.40-4.29 (m, 1 H), 4.26 (t, J=6.8 Hz, 2 H), 3.14 (s, 3 H), 3.05 (t, J=6.8 Hz, 2 H), 3.02-2.89 (m, 2 H), 2.85-2.68 (m, 2 H), 2.44 (s, 3 H). m/z (APCI+) for C12H16ClF2N3O3S2 388.0 (M+H)+.

Workup

washThe reaction mixture was washed with water (3×)
dry with materialthe organic layer was dried (Na2SO4)
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-ccf407a8d7524fdf90c7790bc60a5f31
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260439B2

Reaction notes

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