Methanesulfonyl chloride → HCID 59321424, compound

HRID 1800832Notes

Reaction equation

HRID 1800832 reaction equation
[F:1][C:2]1[C:3]([C:22]([NH:24][CH2:25][C:26]2([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[O:23])=[N:4][CH:5]=[CH:6][C:7]=1[S:8][C:9]1[S:13][C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][N:16]=2)=[N:11][CH:10]=1.[CH3:38][S:39](Cl)(=[O:41])=[O:40].C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1.O.C(#N)C>[F:1][C:2]1[C:3]([C:22]([NH:24][CH2:25][C:26]2([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:27][CH2:28][N:29]([S:39]([CH3:38])(=[O:41])=[O:40])[CH2:30][CH2:31]2)=[O:23])=[N:4][CH:5]=[CH:6][C:7]=1[S:8][C:9]1[S:13][C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][N:16]=2)=[N:11][CH:10]=1

Participants

7

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 250328563-Fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)-N-((4-phenylpiperidin-4-yl)methyl)picolinamide

Product 1

HCID 59321424HCID 59321424, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

3-Fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)-N-((4-phenylpiperidin-4-yl)methyl)picolinamide (crude from deprotection of 3-fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)-N-((4-phenylpiperidin-4-yl)methyl)picolinamide, 0.042 g, 0.066 mmol) was diluted in NMP (1 mL) and treated with methanesulfonyl chloride (0.010 g, 0.086 mmol) and diisopropylethylamine (0.059 mL, 0.331 mmol) at 23° C. The reaction was stirred overnight, then diluted in 10% water in acetonitrile+0.05% TFA and purified on preparative HPLC (acetonitrile/water/trifluoroacetic acid). The fractions containing the desired product were evaporated and the residue was diluted with DMF and applied on a SCX SPE cartridge. This was washed with methanol and eluted with 2M ammonia/methanol/THF. The fractions containing the desired product were concentrated to give a solid (0.0129 g, 32%) which was triturated with ethyl ether, suspended in acetonitrile and treated with a 0.1N hydrochloric acid/methanol solution (0.210 mL). The solution was diluted with water and concentrated on speedvac to give the HCl salt of the title material. 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.92 (1H, ddd, J=13.58, 10.04 and 3.41 Hz), 2.25 (2H, dd, J=13.14 and 3.79 Hz), 2.31 (3H, s), 2.76-2.84 (4H, m), 2.86 (3H, s), 6.84-6.88 (1H, br d), 6.93 (1H, s), 7.03 (1H, t, J=5.31 Hz), 7.11-7.16 (2H, m), 7.23-7.29 (2H, m), 7.36-7.45 (3H, m), 7.81 (1H, s), 8.17 (1H, d, J=5.05 Hz), 8.22 (1H, d, J=5.05 Hz), 8.28 (1H, t, J=6.32 Hz), 11.84 (1H, s). LC/MS (M+H)+: 613. HPLC ret. time (Condition C): 5.588 min.

Workup

  1. custompurified on preparative HPLC (acetonitrile/water/trifluoroacetic acid)
  2. additionThe fractions containing the desired product
  3. customwere evaporated
  4. additionthe residue was diluted with DMF
  5. washThis was washed with methanol
  6. washeluted with 2M ammonia/methanol/THF
  7. additionThe fractions containing the desired product
  8. concentrationwere concentrated

Sources & evidence

ORD record
ord-d79e5afd84fe4db5b4a08eff96f56625
Source dataset
uspto-grants-2013_01
Patent number
US08343999B2

Reaction notes

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