Methanesulfonyl chloride → US10023592, Example 41

HRID 518280Notes

Reaction equation

HRID 518280 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:26])=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]4[CH:19]=[N:20][N:21]([CH3:23])[CH:22]=4)[CH:16]=3)[C:11](=[O:24])[N:10]([CH3:25])[CH:9]=2)[CH:7]=1.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>N1C=CC=CC=1.C(Cl)Cl>[F:26][C:5]1[CH:4]=[CH:3][C:2]([NH:1][S:28]([CH3:27])(=[O:30])=[O:29])=[CH:7][C:6]=1[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:18]3[CH:19]=[N:20][N:21]([CH3:23])[CH:22]=3)[CH:16]=2)[C:11](=[O:24])[N:10]([CH3:25])[CH:9]=1

Participants

5

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 1180221374-(5-Amino-2-fluorophenyl)-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-one

Product 1

HCID 118021649US10023592, Example 41Yield 85.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

4-(5-Amino-2-fluorophenyl)-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-one (25 mg, 0.07 mmol) in pyridine (0.1 mL) and anhydrous CH2Cl2 (0.3 mL) was treated with methanesulfonyl chloride (0.007 mL, 0.09 mmol) in a manner similar to Example 33. After a similar work up, silica gel chromatography, eluting with 50-100% EA in hexane over 4 min and continuing isocratic 100% EA, gave the title compound (24 mg, 0.06 mmol) as a white solid in 78% yield. 1H NMR (400 MHz, DMSO-d6) δ 3.06 (s, 3H), 3.56 (s, 3H), 3.85 (s, 3H), 7.22-7.45 (m, 4H), 7.59 (s, 1H), 7.76 (dd, J=8.34, 1.52 Hz, 1H), 7.85 (s, 1H), 8.16 (s, 1H), 8.29 (d, J=8.34 Hz, 1H), 9.82 (s, 1H). LCMS (M+H)+ 427.

Workup

  1. washAfter a similar work up, silica gel chromatography, eluting with 50-100% EA in hexane over 4 min

Sources & evidence

ORD record
ord-01e36a3f0afe45f4b80867e2fa7adc8a
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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