Chlorosulfonic acid → 4-[(R)-2-cyclopentyl-1-(5-methoxy-thiazolo[5,4-b]pyridin-2-ylcarbamoyl)-ethyl]benzenesulfonyl chloride

HRID 889596Notes

Reaction equation

HRID 889596 reaction equation
[Cl:1][S:2]([OH:5])(=O)=[O:3].[CH:6]1([CH2:11][C@H:12]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:13]([NH:15][C:16]2[S:17][C:18]3[C:23]([N:24]=2)=[CH:22][CH:21]=[C:20]([O:25][CH3:26])[N:19]=3)=[O:14])[CH2:10][CH2:9][CH2:8][CH2:7]1>C(Cl)Cl>[CH:6]1([CH2:11][C@H:12]([C:27]2[CH:32]=[CH:31][C:30]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:29][CH:28]=2)[C:13](=[O:14])[NH:15][C:16]2[S:17][C:18]3[C:23]([N:24]=2)=[CH:22][CH:21]=[C:20]([O:25][CH3:26])[N:19]=3)[CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

4

Reactant 2

HCID 24638Chlorosulfonic acidHCID 86625463(R)-3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-phenyl-propionamide

Product 1

HCID 866254644-[(R)-2-cyclopentyl-1-(5-methoxy-thiazolo[5,4-b]pyridin-2-ylcarbamoyl)-ethyl]benzenesulfonyl chloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Chlorosulfonic acid (20 mL) is cooled to 0° C. To this is added a solution of the title F compound, (R)-3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-phenyl-propionamide (2.53 g, 6.632 mmol) in DCM (10 mL). The reaction is allowed to stir and warm to RT over 2.5 h. The reaction is then added dropwise to crushed ice (400 mL) and extracted with DCM (3×100 mL). Extracts are combined, dried over anhydrous sodium sulfate, filtered, and concentrated to give 4-[(R)-2-cyclopentyl-1-(5-methoxy-thiazolo[5,4-b]pyridin-2-ylcarbamoyl)-ethyl]benzenesulfonyl chloride as a yellow foam. Product is isolated as a 80:20 mixture of the desired para product and undesired meta product: 1H NMR (400 MHz, DMSO-D6) 1.1 (s, 2 H) 1.4 (d, J=4.8 Hz, 1 H) 1.4 (s, 1 H) 1.5 (m, 3 H) 1.7 (s, 2 H) 1.8 (d, J=13.4 Hz, 1 H) 2.1 (m, 1 H) 3.9 (s, 3 H) 4.0 (s, 1 H) 6.9 (d, J=8.6 Hz, 1 H) 7.3 (m, 2 H) 7.6 (d, J=8.1 Hz, 2 H) 8.0 (d, J=8.6 Hz, 1 H) 14.3 (s, 2 H); LC/MS 480.2 (M+1), 478.3 (M−1).

Workup

  1. additionThe reaction is then added dropwise
  2. extractionextracted with DCM (3×100 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5d4eddb0dffa4918af2f36cff78383f7
Source dataset
uspto-grants-2012_08
Patent number
US08252931B2

Reaction notes

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