Methanesulfonyl chloride → (1S,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexyl methanesulfonate

HRID 1848218Notes

Reaction equation

HRID 1848218 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:28]=[CH:27][C:15]4[N:16]=[C:17]([NH:19][C@@H:20]5[CH2:25][CH2:24][CH2:23][CH2:22][C@@H:21]5[OH:26])[S:18][C:14]=4[CH:13]=3)[C:5]2=[N:6][CH:7]=1.[CH3:29][S:30](Cl)(=[O:32])=[O:31].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:29][S:30]([O:26][C@H:21]1[CH2:22][CH2:23][CH2:24][CH2:25][C@H:20]1[NH:19][C:17]1[S:18][C:14]2[CH:13]=[C:12]([CH2:11][N:8]3[C:5]4=[N:6][CH:7]=[C:2]([F:1])[CH:3]=[C:4]4[N:10]=[CH:9]3)[CH:28]=[CH:27][C:15]=2[N:16]=1)(=[O:32])=[O:31]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chloride2×HCID 516892Sodium BicarbonateHCID 86681159(1S,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

Product 1

HCID 86681195(1S,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexyl methanesulfonateYield 44.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred mixture of (1R,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (517 mg, 1.3 mmol) from Example 162, TEA (194 μL, 1.4 mmol), and CH2Cl2 (15 mL) at rt under argon was added methanesulfonyl chloride (152 μL, 2.0 mmol). After stirring the mixture for 15 h, additional TEA (194 μL, 1.4 mmol) and methanesulfonyl chloride (152 μL, 2.0 mmol) were added. After stirring for an additional 18 h, the mixture was diluted with CH2Cl2 and stirred with saturated aq NaHCO3 (50 mL) for 30 min. The layers were separated and the organic layer was washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography, eluting with a gradient of 100% hexanes to 100% EtOAc, to afford (1S,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexyl methanesulfonate (274 mg, 44%) as a clear oil. 1H NMR (500 MHz, DMSO-d6) δ 8.66 (s, 1H), 8.39 (t, J=1.8 Hz, 1H), 8.16 (d, J=7.4 Hz, 1H), 8.04 (dd, J=2.6, 9.5 Hz, 1H), 7.66 (d, J=1.0 Hz, 1H), 7.33 (d, J=8.1 Hz, 1H), 7.22 (dd, J=1.4, 8.2 Hz, 1H), 5.46 (s, 2H), 4.98 (m, 1H), 4.06 (m, 1H), 2.99 (s, 3H), 2.01 (m, 1H), 1.54-1.72 (m, 4H), 1.34-1.50 (m, 3H); LCMS (ESI) m/z 476 (M+H)+.

Workup

  1. stirringAfter stirring for an additional 18 h
  2. customThe layers were separated
  3. washthe organic layer was washed with brine (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography
  8. washeluting with a gradient of 100% hexanes to 100% EtOAc

Sources & evidence

ORD record
ord-89a6116bc51a408e8baab40d38a91c24
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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