Hydrochloric Acid → HCID 67045751, compound

HRID 875727Notes

Reaction equation

HRID 875727 reaction equation
[Br:1][C:2]1[C:3]([N:21]2[CH2:26][CH2:25][CH2:24][C@@H:23]([NH:27]C(=O)OC(C)(C)C)[CH2:22]2)=[C:4]2[C:10]([NH:11][C:12]([C:14]3([C:17]([F:20])([F:19])[F:18])[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[ClH:35]>C(O)(C(F)(F)F)=O.CO.CCOCC>[ClH:35].[NH2:27][C@@H:23]1[CH2:24][CH2:25][CH2:26][N:21]([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:14]4([C:17]([F:18])([F:19])[F:20])[CH2:16][CH2:15]4)=[O:13])[C:4]=23)[CH2:22]1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 67045323HCID 67045323, compound

Product 1

HCID 67045751HCID 67045751, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

(R)-tert-Butyl 1-(5-bromo-3-(1-(trifluoromethyl)cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (65 mg, 0.12 mmol) in TFA (5 mL) was stirred at room temperature for 1.5 hours and concentrated in vacuo. The residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 12M column, 3-65% CH3CN/water gradient; 14 CV). The residue obtained was dissolved in minimal methanol, and 2N HCl in ether was added. The precipitate formed was filtered and dried under high vacuum to yield (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-(trifluoromethyl)cyclopropanecarboxamide hydrochloride (58 mg, 94% yield). 1H NMR (400 MHz, (CD3)2SO) δ 11.97 (br s, 1H), 9.32 (s, 1H), 8.39 (s, 2H), 8.27 (s, 1H), 7.63 (s, 1H), 3.50-3.22 (m, 4H), 3.15-3.04 (m, 1H), 2.20-2.10 (m, 1H), 1.90-1.78 (m, 1H), 1.76-1.46 (m, 4H), 1.36-1.44 (m, 2H); LCMS (APCI+) m/z 429.2, 446.1, 448.0 (M+H)+, Retention time=2.07 minutes (Method 3).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit
  3. customThe residue obtained
  4. customThe precipitate formed
  5. filtrationwas filtered
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-815797d0523f41cbbbca9fb7bf1357d5
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

Loading…