Hydrochloric Acid → HCID 58379668, compound

HRID 1038992Notes

Reaction equation

HRID 1038992 reaction equation
[C@H:1]1([N:10]([C:39](=[O:45])[C:40]([CH3:44])([CH3:43])[CH2:41][F:42])[CH2:11]/[CH:12]=[CH:13]/[C:14]2[CH:15]=[C:16]3[CH2:38][C@@:21]4([C:29]5[C:24](=[N:25][CH:26]=[CH:27][CH:28]=5)[N:23](C(OC(C)(C)C)=O)[C:22]4=[O:37])[CH2:20][C:17]3=[N:18][CH:19]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.Cl.[OH-].[Na+]>CN(C=O)C>[C@H:1]1([N:10]([CH2:11]/[CH:12]=[CH:13]/[C:14]2[CH:15]=[C:16]3[CH2:38][C@@:21]4([C:29]5[C:24](=[N:25][CH:26]=[CH:27][CH:28]=5)[NH:23][C:22]4=[O:37])[CH2:20][C:17]3=[N:18][CH:19]=2)[C:39](=[O:45])[C:40]([CH3:44])([CH3:43])[CH2:41][F:42])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58379692HCID 58379692, compound

Product 1

HCID 58379668HCID 58379668, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of tert-butyl (6S)-3-{(1E)-3-[(1R)-2,3-dihydro-1H-inden-1-yl(3-fluoro-2,2-dimethylpropanoyl)amino]prop-1-en-1-yl}-2′-oxo-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-1′(2′H)-carboxylate (130 mg, 0.213 mmol, described in step F) in DMF (2 mL) was added 1 N aqueous HCl (6.4 mL, 6.39 mmol). The reaction was stirred at ambient temperature and upon completion 1 N aqueous NaOH (4 mL) was added to bring to an approximately neutral pH. The mixture was then partitioned between 5% sodium bicarbonate and DCM. The organics were then washed once with half-saturated brine. The organics were dried over sodium sulfate, filtered, and concentrated in vacuo to provide a residue which still contained a considerable quantity of DMF. This residue was purified by reverse phase HPLC eluting with MeCN/Water (0.1% TFA). The product containing fractions were pooled, and neutralized with 10% NH4OH in MeOH. The bulk of the organics were then removed in vacuo, and the remaining mostly aqueous layer was extracted twice with DCM. The DCM solution was dried over sodium sulfate, filtered, and concentrated in vacuo to provide the title compound. MS: m/z=511 (M+1). Human CGRP receptor binding Ki=0.060 nM. HRMS: m/z=551.2517; calculated m/z=551.2504 for C31H31FN4O2.

Workup

  1. additionwas added
  2. customThe mixture was then partitioned between 5% sodium bicarbonate and DCM
  3. washThe organics were then washed once with half-saturated brine
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto provide a residue which
  8. customThis residue was purified by reverse phase HPLC
  9. washeluting with MeCN/Water (0.1% TFA)
  10. additionThe product containing fractions
  11. customThe bulk of the organics were then removed in vacuo
  12. extractionthe remaining mostly aqueous layer was extracted twice with DCM
  13. dry with materialThe DCM solution was dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c02d225e71a24fb09cecd6c345939a65
Source dataset
uspto-grants-2013_10
Patent number
US08552023B2

Reaction notes

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