Citric Acid → HCID 57537565, compound

HRID 1693739Notes

Reaction equation

HRID 1693739 reaction equation
C([O:3][C:4](=O)[C:5]1[CH:10]=[C:9]([C:11]2[C:12]([Cl:37])=[C:13]3[C:19]([C:20]4[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=4[O:27][CH3:28])=[CH:18][N:17]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[C:14]3=[N:15][CH:16]=2)[CH:8]=[N:7][CH:6]=1)C.[OH-].[K+].Cl.[CH:42]([N:45](C(C)C)[CH2:46]C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CNC.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO.O.C1COCC1.ClCCl>[Cl:37][C:12]1[C:11]([C:9]2[CH:8]=[N:7][CH:6]=[C:5]([CH:10]=2)[C:4]([N:45]([CH3:46])[CH3:42])=[O:3])=[CH:16][N:15]=[C:14]2[N:17]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:34])[CH3:35])[CH:18]=[C:19]([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=3[O:27][CH3:28])[C:13]=12

Participants

12

Reactant 7

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 674DimethylamineHCID 14797Potassium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57537546HCID 57537546, compound

Product 1

HCID 57537565HCID 57537565, compoundYield 37.5%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

68 mg (0.12 mmol) of 5-[4-chloro-3-(5-fluoro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-nicotinic acid ethyl ester was dissolved in methanol and 100 μL of 50% w/v of potassium hydroxide in water was added. The resulting mixture was left at room temperature for 8 h. The mixture was adjusted to pH 3 by addition of 100 μL of concentrated aqueous hydrochloric acid and the solvent completely evaporated. The residue was dissolved in 50 mL of 50% v/v methanol in diethyl ether. The insoluble residue was filtered off and the filtrate evaporated. The resulting material was dissolved in 10 mL of 50% v/v acetonitrile in dichloromethane. 100 μL (0.57 mmol) of di-iso-propylethylamine was added, followed by 92 mg (0.24 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate. The resulting suspension was sonicated until a homogeneous solution was obtained. 0.5 mL (1 mmol) of a 2 M solution of dimethylamine in anhydrous THF was added and the resulting mixture left at ambient temperature for 24 h. The resulting solution was distributed between dichloromethane and 10% w/v aqueous citric acid solution. The organic phase was dried over sodium sulfate and evaporated to afford 24 mg (45 μmol, 37%) of 5-[4-chloro-3-(5-fluoro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-nicotinamide. 1H-NMR [500 MHz, d6-DMSO] δ: 8.75 (d, 1H), 8.71 (d, 1H), 8.27 (s, 1H), 7.89 (t, 1H), 7.42 (s, 1H), 7.27 (s, 1H), 7.09-7.03 (m, 2H), 6.86 (dd, 1H), 5.74 (s, 2H), 3.74 (s, 3H), 3.64 (t, 2H), 3.15 (s, 3H), 3.08 (s, 3H), 0.97 (t, 2H), −0.2 (s, 9H); MS [MH+] m/z: 555.2.

Workup

  1. additionwas added
  2. customthe solvent completely evaporated
  3. dissolutionThe residue was dissolved in 50 mL of 50% v/v methanol in diethyl ether
  4. filtrationThe insoluble residue was filtered off
  5. customthe filtrate evaporated
  6. dissolutionThe resulting material was dissolved in 10 mL of 50% v/v acetonitrile in dichloromethane
  7. customThe resulting suspension was sonicated until a homogeneous solution
  8. customwas obtained
  9. waitthe resulting mixture left at ambient temperature for 24 h
  10. dry with materialThe organic phase was dried over sodium sulfate
  11. customevaporated

Sources & evidence

ORD record
ord-7cd42ecd7e9d428ab70ea16f9198b10a
Source dataset
uspto-grants-2012_04
Patent number
US08158647B2

Reaction notes

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