Potassium Carbonate → tert-butyl ({1-[(2S)-bicyclo[2.2. l]hept-2-yl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl}methyl)(methylsulfonyl)carbamate

HRID 712011Notes

Reaction equation

HRID 712011 reaction equation
[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[N:8]1[C:12]2=[C:13]3[S:19][CH:18]=[CH:17][C:14]3=[N:15][CH:16]=[C:11]2[N:10]=[C:9]1[CH2:20]Cl.[CH3:22][S:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])(=[O:25])=[O:24].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[N:8]1[C:12]2=[C:13]3[S:19][CH:18]=[CH:17][C:14]3=[N:15][CH:16]=[C:11]2[N:10]=[C:9]1[CH2:20][N:26]([S:23]([CH3:22])(=[O:24])=[O:25])[C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 10081367tert-Butyl methylsulfonylcarbamateHCID 867174691-[(2S)-Bicyclo[2.2.1]hept-2-yl]-2-(chloromethyl)-1H-imidazo[4,5-d]thieno[3,2-b]pyridine

Product 1

HCID 86717470tert-butyl ({1-[(2S)-bicyclo[2.2. l]hept-2-yl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl}methyl)(methylsulfonyl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-[(2S)-bicyclo[2.2.1]hept-2-yl]-2-(chloromethyl)-1H-imidazo[4,5-d]thieno[3,2-b]pyridine (0.10 g, 0.31 mmol) dissolved in N,N-dimethylformamide (1 mL) was added tert-butyl (methylsulfonyl)carbamate (0.092 g, 0.47 mmol) and potassium carbonate (0.087 g, 0.63 mmol). The mixture was stirred at 50° C. overnight, then diluted with water and extracted with EtOAc. The combined organic layers were dried over MgSO4 and concentrated to give crude tert-butyl ({1-[(2S)-bicyclo[2.2. l]hept-2-yl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl}methyl)(methylsulfonyl)carbamate. LCMS calculated for C22H29N4O4S2 (M+H)+: m/z=477.2. Found: 477.1. The crude intermediate was treated with trifluoroacetic acid (0.5 mL, 6 mmol) in methylene chloride (0.5 mL) at room temperature for 30 min, then the solvent was removed in vacuo. The residue was re-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 (30 mg, 25%). LCMS calculated for C17H21N4O2S2 (M+H)+: m/z=377.1. Found: 377.0.

Workup

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

Sources & evidence

ORD record
ord-3f3a779549194d2fb386737c3f96520e
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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