Hydrochloric Acid → HCID 73890914, compound

HRID 1483045Notes

Reaction equation

HRID 1483045 reaction equation
[O:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[O:4][C@@H:3]([CH2:11][NH2:12])[CH2:2]1.[F:13][C:14]([F:30])([F:29])[C@@H:15]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[C:16]1[CH:21]=[CH:20][C:19]([CH:22]=O)=[CH:18][CH:17]=1.[BH4-].[Na+].[ClH:33]>C(Cl)Cl.CO>[ClH:33].[O:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[O:4][C@@H:3]([CH2:11][NH:12][CH2:22][C:19]2[CH:18]=[CH:17][C:16]([C@H:15]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[C:14]([F:29])([F:30])[F:13])=[CH:21][CH:20]=2)[CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 68531823[(3S)-2,3-Dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl]methanamineHCID 86691246HCID 86691246, compound

Product 1

HCID 73890914HCID 73890914, compoundYield 47.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Combine [(3S)-2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-3-YL]methanamine (9.71 g, 58.4 mmol), N-[(1S)-2,2,2-trifluoro-1-(4-formylphenyl)-ethyl]-methanesulfonamide (16.43 g, 58.4 mmol) and MeOH (292 mL). Add 4 Å Molecular Sieves (30 mL) and stir the mixture at ambient temperature under a nitrogen atmosphere for 1 h. Add sodium borohydride (8.84 g, 233.7 mmol) portionwise and stir at ambient temperature for 10 minutes, monitoring the reaction via MS and 1H NMR. Slowly add H2O to quench the reaction and filter through Celite®. Collect the filtrate; remove solvents under reduced pressure; and purify via flash column chromatography using a gradient of 0-100% of (5% (2N NH3/MeOH) in DCM) in (5% MeOH/DCM) to elute the product. Combine the product fractions, and remove solvents under reduced pressure to afford the free base as a residue. Dissolve the residue in DCM, and add HCl (1N in Et2O; 87.7 mL, 87.7 mmol) while stirring. Stir for 10 minutes after the addition is complete, then remove the solvents under reduced pressure to provide the title product (12.9 g, 47.3%) as a white solid. MS (m/z): 432 (M-Cl).

Workup

  1. additionAdd 4 Å Molecular Sieves (30 mL)
  2. customthe reaction via MS and 1H NMR
  3. customSlowly add H2O to quench
  4. customthe reaction
  5. filtrationfilter through Celite®
  6. customCollect the filtrate
  7. customand purify via flash column chromatography
  8. washto elute the product
  9. customremove solvents under reduced pressure
  10. customto afford the free base as a residue
  11. stirringwhile stirring
  12. stirringStir for 10 minutes
  13. additionafter the addition
  14. customremove the solvents under reduced pressure

Sources & evidence

ORD record
ord-3bce46b91ea048958cb303368ae130a7
Source dataset
uspto-grants-2016_08
Patent number
US09416138B2

Reaction notes

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