Citric Acid → HCID 67198895, compound

HRID 510009Notes

Reaction equation

HRID 510009 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[C:21]4[C:27]([CH2:28][C:29]5[C:30]([F:46])=[N:31][C:32]([NH:35][CH2:36][C:37]6[C:38]([O:44][CH3:45])=[N:39][CH:40]=[C:41]([F:43])[CH:42]=6)=[CH:33][CH:34]=5)=[CH:26][N:25](S(C5C=CC=CC=5)(=O)=O)[C:22]4=[N:23][CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.[OH-].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(OC(N1CCC(N2C=C(C3C=C4C(CC5C(F)=NC(NCC6C(OC)=NC=C(F)C=6)=CC=5)=CNC4=NC=3)C=N2)CC1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>CO.ClCCl>[F:43][C:41]1[CH:42]=[C:37]([CH2:36][NH:35][C:32]2[CH:33]=[CH:34][C:29]([CH2:28][C:27]3[C:21]4[C:22](=[N:23][CH:24]=[C:19]([C:17]5[CH:16]=[N:15][N:14]([CH:11]6[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]6)[CH:18]=5)[CH:20]=4)[NH:25][CH:26]=3)=[C:30]([F:46])[N:31]=2)[C:38]([O:44][CH3:45])=[N:39][CH:40]=1

Participants

9

Reactant 6

HCID 311Citric AcidHCID 6422Trifluoroacetic acidHCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 67198589HCID 67198589, compoundHCID 67200881HCID 67200881, compound

Product 1

HCID 67198895HCID 67198895, compoundYield 78.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

In a vial, 4-[4-(1-benzenesulfonyl-3-{2-fluoro-6-[(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]-pyridin-3-ylmethyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (170, 0.137 g, 0.178 mmol) was dissolved in a solution of potassium hydroxide (0.392 g, 6.99 mmol) in 7.0 mL of methanol and the reaction was heated at 50° C. for 3 hours. Aqueous 1 M citric acid was added, then the reaction was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. 4-[4-(3-{2-fluoro-6-[(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]-pyridin-3-ylmethyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (P-1702, 56 mg, 0.0888 mmol) was combined with this and 10 mL of dichloromethane and trifluoroacetic acid (0.50 mL, 6.5 mmol) were added, then stirred at room temperature for 2 hours. Aqueous saturated sodium bicarbonate was added to pH=8, then concentrated under vacuum and ethyl acetate and water were added. The organic layer was isolated and washed with aqueous saturated sodium bicarbonate, then dried with magnesium sulfate, filtered and the filtrate concentrated under vacuum to provide the desired compound as a yellow solid (P-1703, 74 mg). MS (ESI) [M+H+]+=631.1.

Workup

  1. extractionthe reaction was extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under vacuum
  6. additionwere added
  7. concentrationconcentrated under vacuum and ethyl acetate and water
  8. additionwere added
  9. customThe organic layer was isolated
  10. washwashed with aqueous saturated sodium bicarbonate
  11. dry with materialdried with magnesium sulfate
  12. filtrationfiltered
  13. concentrationthe filtrate concentrated under vacuum

Sources & evidence

ORD record
ord-7b15353e77b249b2b45ebabc023ad9ad
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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