Dichloromethane → (R)-N-(4-(3-aminopiperidin-1-yl)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazine-2-carboxamide hydrochloride

HRID 408262Notes

Reaction equation

HRID 408262 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]([NH:9][C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([C:33]([F:36])([F:35])[F:34])[C:17]=2[N:19]2[CH2:24][CH2:23][CH2:22][C@@H:21]([NH:25]C(=O)OC(C)(C)C)[CH2:20]2)[NH:12][CH:11]=1)=[O:8].C(O)(C(F)(F)F)=O.C(Cl)[Cl:45]>>[ClH:45].[NH2:25][C@@H:21]1[CH2:22][CH2:23][CH2:24][N:19]([C:17]2[C:16]([C:33]([F:35])([F:36])[F:34])=[CH:15][N:14]=[C:13]3[NH:12][CH:11]=[C:10]([NH:9][C:7]([C:2]4[CH:3]=[N:4][CH:5]=[CH:6][N:1]=4)=[O:8])[C:18]=23)[CH2:20]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 67045857(R)-tert-butyl 1-(3-(pyrazine-2-carboxamido)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045324(R)-N-(4-(3-aminopiperidin-1-yl)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazine-2-carboxamide hydrochlorideYield 62%

Procedure

(R)-tert-Butyl 1-(3-(pyrazine-2-carboxamido)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.120 g, 0.237 mmol) was placed in DCM (3 mL) at room temperature. TFA (1 mL) was then added, and the reaction was stirred at room temperature for 1 hour. The reaction was then concentrated to dryness to give the crude product, which was purified C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 0-50% CH3CN/water gradient; 25 CV). The purified product was then dissolved in DCM (with minimal MeOH to aid solubility) and added dropwise to a stirring solution of 1M HCl in ether. The resulting solid was filtered, dried and collected to give (R)—N-(4-(3-aminopiperidin-1-yl)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazine-2-carboxamide hydrochloride (0.071 g, 62% yield). 1H NMR (400 MHz, D2O) δ 8.84 (s, 1H), 8.59-8.59 (m, 1H), 8.52-8.52 (m, 1H), 8.31 (s, 1H), 7.79 (s, 1H), 3.62-3.54 (m, 1H), 3.37-3.33 (m, 1H), 3.00-2.92 (m, 3H), 2.04-2.01 (m, 1H), 1.85-1.72 (m, 1H), 1.71-1.66 (m, 1H), 1.50-1.40 (m, 1H); LCMS (APCI+) m/z 406 (M+H)+.

Workup

  1. concentrationThe reaction was then concentrated to dryness
  2. customto give the crude product, which
  3. customwas purified C-18 reverse phase flash chromatography (Biotage SP4 unit
  4. dissolutionThe purified product was then dissolved in DCM (with minimal MeOH to aid solubility)
  5. additionadded dropwise to a stirring solution of 1M HCl in ether
  6. filtrationThe resulting solid was filtered
  7. customdried
  8. customcollected

Sources & evidence

ORD record
ord-1552259691d947e6a1e26a5775277a22
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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