Methanesulfonic Acid → HCID 178458669, compound

HRID 2189835Notes

Reaction equation

HRID 2189835 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([NH:20][C@H:21]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH2:22][OH:23])=[N:5][C:6]([NH:10][C:11]2[CH:15]=[C:14]([O:16][CH:17]([CH3:19])[CH3:18])[NH:13][N:12]=2)=[C:7]([F:9])[CH:8]=1.[CH3:31][S:32](O)(=[O:34])=[O:33].CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C1COCC1>[F:9][C:7]1[CH:8]=[C:3]([CH2:2][NH:1][S:32]([CH3:31])(=[O:34])=[O:33])[C:4]([NH:20][C@H:21]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH2:22][OH:23])=[N:5][C:6]=1[NH:10][C:11]1[CH:15]=[C:14]([O:16][CH:17]([CH3:19])[CH3:18])[NH:13][N:12]=1

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 81531DiisopropylethylamineHCID 178458667HCID 178458667, compound

Product 1

HCID 178458669HCID 178458669, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A round bottom flask was charged with (R)-2-(3-(aminomethyl)-5-fluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)pyridin-2-ylamino)-2-(4-fluorophenyl)ethanol (Example 13; 0.10 g, 0.24 mmol), methanesulfonic acid loaded TFP resin (0.9 mmol/g loading, 0.24 mmol), DIEA (0.062 g, 0.48 mmol), DMAP (0.032 g, 0.26 mmol), and THF (5 ml). The resulting suspension was shaken vigorously at 60° C. for 8 hrs and filtered. The resulting resin was washed with a THF-DCM solution (1:1, 3×5 ml for 30 min. each). The resulting organic layers were combined and concentrated. The resulting solid was purified by reverse-phase column chromatography (5-50% CH3CN in H2O over 400 ml) to give the title compound (0.075 g, 63%). 1H NMR (400 MHz, CD3OD) δ 7.48-7.45 (m, 2H), 7.20 (d, J=10.9 Hz, 1H), 7.05-7.01 (m, 2H), 5.30 (s, 1H), 5.04-5.01 (m, 1H), 4.56-4.53 (m, 1H), 4.20 (d, J=14.4 Hz, 1H), 4.12 (d, J=14.4 Hz, 1H), 3.86-3.73 (m, 2H), 3.01 (s, 3H), 1.32 (d, J=6.0 Hz, 3H). MS: Calcd.: 496. Found: [M+H]+ 497.

Workup

  1. filtrationfiltered
  2. washThe resulting resin was washed with a THF-DCM solution (1:1, 3×5 ml for 30 min. each)
  3. concentrationconcentrated
  4. customThe resulting solid was purified by reverse-phase column chromatography (5-50% CH3CN in H2O over 400 ml)

Sources & evidence

ORD record
ord-3cc0d639de8a41298b2d6cd8dc2a9085
Source dataset
uspto-grants-2012_12
Patent number
US08324252B2

Reaction notes

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