Hydrochloric Acid → HCID 67045397, compound

HRID 875770Notes

Reaction equation

HRID 875770 reaction equation
[Br:1][C:2]1[C:3]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24]C(=O)OC(C)(C)C)[CH2:19]2)=[C:4]2[C:10]([NH:11][C:12](=[O:17])[CH2:13][CH:14]3[CH2:16][CH2:15]3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[ClH:32]>C(O)(C(F)(F)F)=O.C(Cl)Cl.CCOCC>[ClH:32].[NH2:24][C@@H:20]1[CH2:21][CH2:22][CH2:23][N:18]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12](=[O:17])[CH2:13][CH:14]4[CH2:15][CH2:16]4)[C:4]=23)[CH2:19]1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 67045326HCID 67045326, compound

Product 1

HCID 67045397HCID 67045397, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (R)-tert-butyl 1-(5-bromo-3-(2-cyclopropylacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (80 mg, 0.16 mmol) in neat TFA (3 mL) was stirred at room temperature for 30 minutes. TFA was then removed in vacuo. The oily residue obtained was dissolved in few drops of CH2Cl2 and treated with 2M HCl in ether (2 mL). The solid formed was filtered, washed with additional CH2Cl2 (3×3 mL). This material was dissolved in MeOH (0.5 mL), and CH3CN was added until the mixture became cloudy. The mixture was allowed to stand at room temperature. The solid formed was filtered, washed with additional CH3CN (2×2 mL), was dried under a stream of nitrogen first and then under high vacuum to provide (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyclopropylacetamide hydrochloride (32 mg, 42% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 11.81 (s, 1H), 9.25 (s, 1H), 8.23 (s, 1H), 8.22 (br s, 3H), 7.54 (s, 1H), 3.45-3.38 (m, 2H), 3.36-3.26 (m, 2H), 3.10-3.04 (m, 1H), 2.31 (d, 2H), 2.15-2.08 (m, 1H), 1.86-1.79 (m, 1H), 1.72-1.62 (m, 1H), 1.53-1.45 (m, 1H), 1.13-1.06 (m, 1H), 0.54-0.51 (m, 2H), 0.24-0.21 (m, 2H); LCMS (APCI+) m/z 392.1, 394 (M+H)+, Retention time=2.23 minutes (Method 2).

Workup

  1. customTFA was then removed in vacuo
  2. customThe oily residue obtained
  3. customThe solid formed
  4. filtrationwas filtered
  5. washwashed with additional CH2Cl2 (3×3 mL)
  6. dissolutionThis material was dissolved in MeOH (0.5 mL)
  7. additionCH3CN was added until the mixture
  8. customto stand at room temperature
  9. customThe solid formed
  10. filtrationwas filtered
  11. washwashed with additional CH3CN (2×2 mL)
  12. customwas dried under a stream of nitrogen first

Sources & evidence

ORD record
ord-6a8e4867329e4514bfe11c44c1b182f2
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

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