Methanesulfonyl chloride → HCID 86695242, compound

HRID 1504079Notes

Reaction equation

HRID 1504079 reaction equation
FC(F)(F)C(O)=O.[CH3:8][N:9]([CH3:30])[CH:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[C:18]3[C:19]4[CH2:20][NH:21][CH2:22][CH2:23][C:24]=4[S:25][C:26]=3[N:27]=[CH:28][N:29]=2)[CH2:12][CH2:11]1.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>ClCCl>[CH3:31][S:32]([N:21]1[CH2:20][C:19]2[C:18]3[C:17]([O:16][CH:13]4[CH2:12][CH2:11][CH:10]([N:9]([CH3:30])[CH3:8])[CH2:15][CH2:14]4)=[N:29][CH:28]=[N:27][C:26]=3[S:25][C:24]=2[CH2:23][CH2:22]1)(=[O:34])=[O:33]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 86695243HCID 86695243, compound

Product 1

HCID 86695242HCID 86695242, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N,N-dimethyl-4-[8-thia-4,6,12-triazatricyclo[7.4.0.0-[2,7]]trideca-1(9),2(7),3,5-tetraen-3-yloxy]cyclohexan-1-amine trifluoroacetate (30 mg, 0.09 mmol, 1.00 equiv) in 5 mL of anhydrous dichloromethane was added TEA (40 mg, 0.40 mmol, 4.38 equiv) and MsCl (14 mg, 0.12 mmol, 1.36 equiv) at 0° C. under nitrogen. The resulting solution was stirred for 2 h at room temperature. The reaction mixture was concentrated under vacuum and the residue was purified by preparative HPLC under the following conditions (Waters): Column: XBridge Prep C18 OBD Column, 5 μm, 19*150 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (16% CH3CN increasing to 23% in 10 min, up to 100% in 2 min, down to 16% in 2 min); flow rate: 20 mL/min; UV Detection at 254/220 nm. This resulted in 8.0 mg (22%) of 4-([12-methanesulfonyl-8-thia-4,6,12-triazatricyclo[7.4.0.0-[2,7]]trideca-1(9),2(7),3,5-tetraen-3-yl]oxy)-N,N-dimethylcyclohexan-1-amine as a white solid. MS (ES): m/z 411 (M+H)+; 1H NMR (300 MHz, CD3OD): δ 1.59-1.71 (m, 4H), 2.05-2.10 (d, 2H, J=15 Hz), 2.34-2.50 (m, 9H), 2.98 (s, 3H), 3.08 (t, 2H, J=5.7 Hz), 3.06 (t, 2H, J=5.7 Hz), 4.67 (t, 2H, J=1.8 Hz), 5.26 (m, 1H), 8.53 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe residue was purified by preparative HPLC under the following conditions (Waters)
  3. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (16% CH3CN increasing to 23% in 10 min
  4. waitup to 100% in 2 min
  5. waitdown to 16% in 2 min)
  6. customThis resulted in 8.0 mg (22%) of 4-([12-methanesulfonyl-8-thia-4,6,12-triazatricyclo[7.4.0.0-[2,7]]trideca-1(9),2(7),3,5-tetraen-3-yl]oxy)-N,N-dimethylcyclohexan-1-amine as a white solid

Sources & evidence

ORD record
ord-fba7b53fd0014848b4ff011ff5980dc2
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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