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

HRID 1806040Notes

Reaction equation

HRID 1806040 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-f830f5187d434e04bd6900df630458a8
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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