Methanesulfonyl chloride → tert-butyl(3S)-3-{[6-chloro-2-(methylsulfanyl)-5-{2-[(methylsulfonyl)oxy]ethyl}pyrimidin-4-yl]amino}-3-methylpyrrolidine-1-carboxylate

HRID 1775491Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([NH:10][C@@:11]2([CH3:23])[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]2)[C:3]=1[CH2:24][CH2:25][OH:26].[CH3:27][S:28](Cl)(=[O:30])=[O:29]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([NH:10][C@@:11]2([CH3:23])[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:12]2)[C:3]=1[CH2:24][CH2:25][O:26][S:28]([CH3:27])(=[O:30])=[O:29]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of tert-butyl(3S)-3-{[6-chloro-5-(2-hydroxyethyl)-2-(methylsulfanyl)pyrimidin-4-yl]amino}-3-methylpyrrolidine-1-carboxylate (1.37 g, 3.40 mmol) in DCM (57 mL) was added TEA (1.66 mL, 11.9 mmol), methanesulfonylchloride (0.7 mL, 8.5 mmol) and DMAP (25 mg, 0.204 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h and then at room temperature for 1 h. The reaction mixture was transferred to a separatory funnel with the aid of DCM. The solution was washed with water (3 times), dried over Na2SO4 and concentrated to give 1.86 g (>99%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 6.90 (d, J=18.5 Hz, 1 H), 4.28-4.19 (m, 2 H), 3.82-3.61 (m, 1 H), 3.60-3.42 (m, 1H), 3.41-3.36 (m, 1 H), 3.32-3.23 (m, 1 H), 3.13 (s, 3 H), 3.12-3.06 (m, 2 H), 2.45 (s, 3 H), 2.41-2.26 (m, 1 H), 2.07-1.97 (m, 1 H), 1.46 (d, J=11.4 Hz, 3 H), 1.38 (s, 9 H). m/z (APCI+) for C18H29ClN4O5S2 481.1 (M+H)+.

Workup

waitat room temperature for 1 h
washThe solution was washed with water (3 times)
dry with materialdried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-aa4789eeafa54b4ab34733d7eae56a59
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260439B2

Reaction notes

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