Citric Acid → HCID 67133393, compound

HRID 659684Notes

Reaction equation

HRID 659684 reaction equation
[CH2:1]([O:5][C:6]([NH:8][S:9]([C:12]1[S:13][C:14]([CH2:33][CH:34]([CH3:36])[CH3:35])=[CH:15][C:16]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][N:24]2C3=NC=CC=C3N=C2)[CH:18]=1)(=[O:11])=[O:10])=[O:7])[CH2:2][CH2:3][CH3:4].B(Cl)(Cl)Cl.[N:41]1([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][N:47]=2)[CH2:45]CCC1.ClC(OCCCC)=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[CH2:1]([O:5][C:6]([NH:8][S:9]([C:12]1[S:13][C:14]([CH2:33][CH:34]([CH3:35])[CH3:36])=[CH:15][C:16]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][N:24]2[C:51]3[C:46](=[N:47][CH:48]=[CH:49][CH:50]=3)[N:41]=[CH:45]2)[CH:18]=1)(=[O:11])=[O:10])=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 25135Boron TrichlorideHCID 61140Butyl chloroformateHCID 110190202-(Pyrrolidin-1-yl)pyridineHCID 67132972HCID 67132972, compound

Product 1

HCID 67133393HCID 67133393, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(3-imidazo[4,5-b]pyridin-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (35.7 mg, 0.074 mmol; see Example 8(b)) in CH2Cl2 (2 mL) was added BCl3 (0.6 mL, 1.0 M in hexane) and the reaction mixture was stirred for 1 h at ambient temperature. The reaction mixture was concentrated in vacuo. Water (5 mL) was added to the residue and this was then extracted with EtOAc. The combined organic phase was washed with water and brine, dried (over anhydrous MgSO4) and concentrated in vacuo. To the crude product dissolved in pyridine (1.5 mL) was added pyrrolidinopyridine (21.9 mg, 0.148 mmol) and butyl chloroformate (94.1 μL, 0.74 mmol) and the reaction mixture was stirred overnight. Citric acid (3 mL, 10% aq) was added to the reaction mixture, which was then extracted with EtOAc, dried (over anhydrous MgSO4), concentrated in vacuo, and the residue purified by flash chromatography using MeOH:CH2Cl2 (5:95) as eluent to give the title compound in 58% yield, over two steps, (22.8 mg, 0.043 mmol).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionWater (5 mL) was added to the residue
  3. extractionthis was then extracted with EtOAc
  4. washThe combined organic phase was washed with water and brine
  5. dry with materialdried (over anhydrous MgSO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionTo the crude product dissolved in pyridine (1.5 mL)
  8. stirringthe reaction mixture was stirred overnight
  9. extractionwas then extracted with EtOAc
  10. dry with materialdried (over anhydrous MgSO4)
  11. concentrationconcentrated in vacuo
  12. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-f396d3aed2eb40069c38de73fda5d316
Source dataset
uspto-grants-2011_12
Patent number
US08080571B2

Reaction notes

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