Hydrochloric Acid → HCID 60205506, compound

HRID 408319Notes

Reaction equation

HRID 408319 reaction equation
[Br:1][C:2]1[C:3]([N:19]2[CH2:24][CH2:23][CH2:22][C@@H:21]([NH:25]C(=O)OC(C)(C)C)[CH2:20]2)=[C:4]2[C:10]([NH:11][C:12]([CH:14]3[CH2:18][CH2:17][CH2:16][O:15]3)=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[ClH:33]>C(O)(C(F)(F)F)=O.CO.C(Cl)Cl.CCOCC>[ClH:33].[NH2:25][C@@H:21]1[CH2:22][CH2:23][CH2:24][N:19]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12]([C@H:14]4[CH2:18][CH2:17][CH2:16][O:15]4)=[O:13])[C:4]=23)[CH2:20]1

Participants

7

Reactant 2

HCID 313Hydrochloric AcidHCID 60205505HCID 60205505, compound

Product 1

HCID 60205506HCID 60205506, compoundYield 21%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl (3R)-1-(5-bromo-3-(tetrahydrofuran-2-carboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate in TFA (3 mL) was stirred at room temperature for 30 minutes and then concentrated in vacuo. The residue obtained was purified by C-18 reverse phase chromatography (Biotage Flash 12 M+, C-18) on Biotage SP4 unit eluting with a gradient of 1-50% CH3CN/water (14 CV). The pure fractions containing the R-isomer (by comparing the retentions times of S-isomer, Example 71A) were pooled, concentrated in vacuo and evaporated from CH3CN (3×5 mL). The solid residue obtained was dissolved in minimal methanol, diluted with CH2Cl2 (1 mL) and treated with 2M HCl in ether (3 mL). The resulting suspension was concentrated in vacuo and evaporated from CH2Cl2 (3×5 mL) and dried under high vacuum for 24 hours to provide (R)—N-(4-((R)-3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)tetrahydrofuran-2-carboxamide hydrochloride (16 mg, 21% yield) as a solid. NMR (400 MHz, (CD3)2SO) δ 11.72 (s, 1H), 9.83 (s, 1H), 8.21 (s, 1H), 8.16 (br s, 3H), 7.89 (s, 1H), 4.37 (t, 1H), 3.96-3.91 (m, 1H), 3.85-3.79 (m, 1H), 3.55-3.48 (m, 3H), 3.26-3.20 (m, 1H), 2.97-2.91 (m, 1H), 2.28-2.20 (m, 1H), 2.15-2.09 (m, 1H), 1.94-1.81 (m, 5H), 1.48-1.40 (m, 1H); LCMS (APCI+) m/z 408.1, 410.1 (M+H)+, Retention time=2.32 minutes (Method 2).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue obtained
  3. customwas purified by C-18 reverse phase chromatography (Biotage Flash 12 M+, C-18) on Biotage SP4 unit
  4. washeluting with a gradient of 1-50% CH3CN/water (14 CV)
  5. additionThe pure fractions containing the R-isomer (
  6. concentrationconcentrated in vacuo
  7. customevaporated from CH3CN (3×5 mL)
  8. customThe solid residue obtained
  9. concentrationThe resulting suspension was concentrated in vacuo
  10. customevaporated from CH2Cl2 (3×5 mL)
  11. customdried under high vacuum for 24 hours

Sources & evidence

ORD record
ord-71a361861f334cecbdbba68badb13b30
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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