Trifluoromethanesulfonyl chloride → HCID 69285757, compound

HRID 75904Notes

Reaction equation

HRID 75904 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([NH:19][C@H:20]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH3:21])=[N:5][C:6]([NH:10][C:11]2[CH:15]=[C:14]([CH:16]3[CH2:18][CH2:17]3)[NH:13][N:12]=2)=[C:7]([F:9])[CH:8]=1.[F:29][C:30]([F:36])([F:35])[S:31](Cl)(=[O:33])=[O:32]>C1COCC1.CN(C1C=CN=CC=1)C>[CH:16]1([C:14]2[NH:13][N:12]=[C:11]([NH:10][C:6]3[N:5]=[C:4]([NH:19][C@H:20]([C:22]4[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=4)[CH3:21])[C:3]([CH2:2][NH:1][S:31]([C:30]([F:36])([F:35])[F:29])(=[O:33])=[O:32])=[CH:8][C:7]=3[F:9])[CH:15]=2)[CH2:18][CH2:17]1

Participants

5

Reactant 2

HCID 79000Trifluoromethanesulfonyl chlorideHCID 67454991(S)-3-(Aminomethyl)-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoro-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,6-diamine

Product 1

HCID 69285757HCID 69285757, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-3-(aminomethyl)-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoro-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,6-diamine (Example 3, 0.10 g, 0.26 mmol) in THF (5 ml) at room temperature was added 1.1 equivalent of trifluoromethylsulfonyl chloride loaded TFP resin, and DMAP (0.031 g, 0.26 mmol). The reaction was then stirred at room temperature for 15 hours and filtered. The remaining resin was then washed with THF (2×10 ml for 20 min), and then combined organic fractions were concentrated. The resulting oil was purified by reverse-phase column chromatography (5-50% ACN) to give the title compound (0.02 g, 15%). 1H NMR (400 MHz, CD3OD) δ 7.40-7.37 (m, 2H), 7.17 (d, J=10.9 Hz, 1H), 7.02-6.97 (m, 2H), 5.90-5.60 (br s, 1H), 5.14-5.12 (m, 1H), 4.28-4.25 (m, 2H), 1.88-1.84 (m, 1H), 1.54 (d, J=7.0 Hz, 3H), 0.95-0.93 (m, 2H), 0.67-0.64 (m, 2H). MS: Calcd.: 516. Found: [M+H]+ 517.

Workup

  1. filtrationfiltered
  2. washThe remaining resin was then washed with THF (2×10 ml for 20 min)
  3. concentrationcombined organic fractions were concentrated
  4. customThe resulting oil was purified by reverse-phase column chromatography (5-50% ACN)

Sources & evidence

ORD record
ord-28c9caed801549edb376875d623ed749
Source dataset
uspto-grants-2014_09
Patent number
US08835465B2

Reaction notes

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