Dichloromethane → HCID 67045285, compound

HRID 875700Notes

Reaction equation

HRID 875700 reaction equation
[Br:1][C:2]1[C:3]([N:20]2[CH2:25][CH2:24][CH2:23][C@@H:22]([NH:26]C(=O)OC(C)(C)C)[CH2:21]2)=[C:4]2[C:10]([NH:11][C:12]([C:14]3[CH:19]=[N:18][CH:17]=[CH:16][N:15]=3)=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:42]>>[ClH:42].[NH2:26][C@@H:22]1[CH2:23][CH2:24][CH2:25][N:20]([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[CH:19]=[N:18][CH:17]=[CH:16][N:15]=4)=[O:13])[C:4]=23)[CH2:21]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 67045070HCID 67045070, compound

Product 1

HCID 67045285HCID 67045285, compoundYield 33%

Procedure

(R)-tert-Butyl 1-(5-bromo-3-(pyrazine-2-carboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.060 g, 0.12 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 and then concentrated to dryness. The resulting residue was purified by reverse phase HPLC (0 to 50% ACN in water, Gilson system). The resulting product was then dissolved in minimal DCM (with MeOH to aid solubility) and added to a stirring solution of 1M HCl in ether. The resulting solid was filtered, washed with ether and dried to give (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazine-2-carboxamide hydrochloride (0.019 g, 33% yield). 1H NMR (400 MHz, D2O) δ 8.69 (s, 1H), 8.57-8.56 (m, 1H), 8.50 (s, 1H), 8.04 (s, 1H), 7.60 (s, 1H), 3.70-3.62 (m, 1H), 3.55-3.50 (m, 1H), 3.42-3.39 (m, 1H), 3.31-3.29 (m, 1H), 2.83-2.80 (m, 1H), 2.19-2.16 (m, 1H), 1.92-1.89 (m, 1H), 1.73-1.69 (m, 1H), 1.49-1.47 (m, 1H); LCMS (APCI+) m/z 416, 418 (M+H)+.

Workup

  1. concentrationconcentrated to dryness
  2. customThe resulting residue was purified by reverse phase HPLC (0 to 50% ACN in water, Gilson system)
  3. dissolutionThe resulting product was then dissolved in minimal DCM (with MeOH to aid solubility)
  4. additionadded to a stirring solution of 1M HCl in ether
  5. filtrationThe resulting solid was filtered
  6. washwashed with ether
  7. customdried

Sources & evidence

ORD record
ord-5554980162a7453581eaa1b447d21358
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

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