Hydrochloric Acid → N-(5-bromo-3-(pyrrolidin-3-yloxy)pyridin-2-yl)-4-methylthiazol-2-amine dihydrochloride

HRID 335107Notes

Reaction equation

HRID 335107 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([O:15][CH:16]2[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17]2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)=[N:6][CH:7]=1.C(Cl)[Cl:29].CO.[ClH:33]>O1CCOCC1>[ClH:29].[ClH:33].[Br:1][C:2]1[CH:3]=[C:4]([O:15][CH:16]2[CH2:20][CH2:19][NH:18][CH2:17]2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 6344DichloromethaneHCID 24764797Tert-butyl 3-(5-bromo-2-(4-methylthiazol-2-ylamino)pyridin-3-yloxy)pyrrolidine-1-carboxylate

Product 1

HCID 24764798N-(5-bromo-3-(pyrrolidin-3-yloxy)pyridin-2-yl)-4-methylthiazol-2-amine dihydrochlorideYield 92.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of tert-butyl 3-(5-bromo-2-(4-methylthiazol-2-ylamino)pyridin-3-yloxy)pyrrolidine-1-carboxylate (prepared according to Example 61; 550 mg, 1.21 mmol) and CH2Cl2 (10 mL) and MeOH (2 mL) was stirred at room temperature. 4N HCl in dioxane (5 mL) was added and the reaction mixture was stirred at room temperature for 30 minutes. The reaction was concentrated and dissolved in small amount of CH2Cl2/methanol and added to vigorously stirred ether and filtered to afford N-(5-bromo-3-(pyrrolidin-3-yloxy)pyridin-2-yl)-4-methylthiazol-2-amine dihydrochloride (478 mg, 92.4% yield) as a white solid. 1H NMR (d6-DMSO) δ 11.18 (bs, 1H), 9.80 (bs, 1H), 9.27 (bs, 1H), 8.09 (d, 1H), 7.83 (d, 1H), 6.80 (s, 1H), 5.42 (m, 1H), 3.62-3.30 (m, 4H), 2.31 (s, 3H), 2.22 (m, 2H); Mass spectrum (apci) m/z=357.0 (M+H-2HCl).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 30 minutes
  2. concentrationThe reaction was concentrated
  3. dissolutiondissolved in small amount of CH2Cl2/methanol
  4. additionadded to vigorously stirred ether
  5. filtrationfiltered

Sources & evidence

ORD record
ord-10f1ad9bf7aa4ebb9146fe78b17ee2e1
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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