Hydrochloric Acid → 1-(3-(5-Bromo-2-(4-methylthiazol-2-ylamino)pyridin-3-yloxy)pyrrolidin-1-yl)ethanone hydrochloride

HRID 335108Notes

Reaction equation

HRID 335108 reaction equation
Cl.Cl.[Br:3][C:4]1[CH:5]=[C:6]([O:17][CH:18]2[CH2:22][CH2:21][NH:20][CH2:19]2)[C:7]([NH:10][C:11]2[S:12][CH:13]=[C:14]([CH3:16])[N:15]=2)=[N:8][CH:9]=1.C(N(CC)CC)C.[C:30]([Cl:33])(=[O:32])[CH3:31].Cl>O.C1COCC1>[ClH:33].[Br:3][C:4]1[CH:5]=[C:6]([O:17][CH:18]2[CH2:22][CH2:21][N:20]([C:30](=[O:32])[CH3:31])[CH2:19]2)[C:7]([NH:10][C:11]2[S:12][CH:13]=[C:14]([CH3:16])[N:15]=2)=[N:8][CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 24764798N-(5-bromo-3-(pyrrolidin-3-yloxy)pyridin-2-yl)-4-methylthiazol-2-amine dihydrochloride

Product 1

HCID 247648001-(3-(5-Bromo-2-(4-methylthiazol-2-ylamino)pyridin-3-yloxy)pyrrolidin-1-yl)ethanone hydrochlorideYield 23.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N-(5-bromo-3-(pyrrolidin-3-yloxy)pyridin-2-yl)-4-methylthiazol-2-amine dihydrochloride (prepared according to Example 62; 70 mg, 0.16 mmol), triethylamine (0.11 mL, 0.82 mmol), and THF (2 mL) was stirred at room temperature. Acetyl chloride (0.009 mL, 0.16 mmol) was added and stirred at room temperature for 30 minutes. Water (15 mL) was added and extracted with EtOAc. The organic layer was dried with sodium sulfate, filtered and concentrated. The residue was purified on silica gel (10% methanol in EtOAc) to afford 1-(3-(5-bromo-2-(4-methylthiazol-2-ylamino)pyridin-3-yloxy)pyrrolidin-1-yl)ethanone hydrochloride (16 mg, 22.56% yield) as a white solid after HCl salt formation. 1H NMR (d6-DMSO) δ 11.60 (bs, 1H), 8.11 (m, 1H), 7.82 (m, 1H), 6.90 (m, 1H), 5.28 (m, 1H), 3.81 (m, 1H), 3.59 (m, 3H), 2.33 (s, 3H), 2.25 (m, 2H), 1.97 (m, 3H); Mass spectrum (apci) m/z=399.1 (M+H—HCl).

Workup

  1. stirringstirred at room temperature for 30 minutes
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on silica gel (10% methanol in EtOAc)

Sources & evidence

ORD record
ord-b1e85461a3a144d28443230fec5e379d
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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