Potassium Carbonate → HCID 178453120, compound

HRID 711997Notes

Reaction equation

HRID 711997 reaction equation
Cl[CH2:2][C:3]1[N:14]([C@H:15]2[CH2:20][CH2:19][C@H:18]([CH2:21][C:22]#[N:23])[CH2:17][CH2:16]2)[C:6]2=[C:7]3[S:13][CH:12]=[CH:11][C:8]3=[N:9][CH:10]=[C:5]2[N:4]=1.[CH3:24][S:25]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])(=[O:27])=[O:26].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[C:22]([CH2:21][C@H:18]1[CH2:19][CH2:20][C@H:15]([N:14]2[C:6]3=[C:7]4[S:13][CH:12]=[CH:11][C:8]4=[N:9][CH:10]=[C:5]3[N:4]=[C:3]2[CH2:2][N:28]([S:25]([CH3:24])(=[O:26])=[O:27])[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:16][CH2:17]1)#[N:23]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 10081367tert-Butyl methylsulfonylcarbamateHCID 178511082HCID 178511082, compound

Product 1

HCID 178453120HCID 178453120, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of {trans-4-[2-(chloromethyl)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-1-yl]cyclohexyl}acetonitrile (from example 17, 22.2 mg, 0.0644 mmol) dissolved in N,N-dimethylformamide (0.2 mL) was added tert-butyl (methylsulfonyl)carbamate (19 mg, 0.096 mmol) and potassium carbonate (18 mg, 0.13 mmol). The reaction was stirred at 50° C. overnight. The mixture was diluted with water, extracted with EtOAc. The combined organic layers were dried over MgSO4 and concentrated to give tert-butyl ({1-[trans-4-(cyanomethyl)cyclohexyl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl}methyl)(methylsulfonyl)carbamate. LCMS calculated for C23H30N5O4S2 (M+H)+: m/z=504.2. Found: 504.1. This crude intermediate was treated with trifluoroacetic acid (0.1 mL, 1 mmol) in methylene chloride (0.1 mL) at room temperature for 30 min, and then the solvent was removed in vacuo. The residue was then dissolved in MeOH and purified on prep-LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (9.5 mg, 36%). LCMS calculated for C18H22N5O2S2 (M+H)+: m/z=404.1. Found: 404.0.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-befd9bce4c0d46fda1bbbd4a85f46e77
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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