Triethylamine → 1-(5-Bromo-4-(4-trifluoromethylthiazol-2-yl)pyridin-2-yl)-3-ethylurea

HRID 1047143Notes

Reaction equation

HRID 1047143 reaction equation
[Br:1][C:2]1[C:3]([C:14]2[S:15][CH2:16][C:17](O)([C:19]([F:22])([F:21])[F:20])[N:18]=2)=[CH:4][C:5]([NH:8][C:9]([NH:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=1.C(N(CC)CC)C.CS(Cl)(=O)=O>O1CCCC1>[Br:1][C:2]1[C:3]([C:14]2[S:15][CH:16]=[C:17]([C:19]([F:21])([F:20])[F:22])[N:18]=2)=[CH:4][C:5]([NH:8][C:9]([NH:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59208483AZD7118 Bromo Trifluoromethyl2×

Product 1

HCID 592083731-(5-Bromo-4-(4-trifluoromethylthiazol-2-yl)pyridin-2-yl)-3-ethylureaYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 1-(5-bromo-4-(4-hydroxy-4-(trifluoromethyl)-4,5-dihydrothiazol-2-yl)pyridin-2-yl)-3-ethylurea (Intermediate 7, 175.8 g, 430 mmol) and triethylamine (295 mL, 2.13 mol) in tetrahydrofuran (3 L) was prepared and stirred at room temperature. Methane sulfonyl chloride (106 mL, 1.36 mol) was added dropwise over the course of an hour. This mixture was stirred at room temperature for 6 hours. The solid was collected by filtration, rinsed with tetrahydrofuran (2×500 mL), and the filtrate was retained while the solid was discarded. The combined tetrahydrofuran layers were concentrated to a viscous, yellow semi-solid which was then washed with water (2×500 mL). This solid was further stirred with water (500 mL) for 18 hours, then filtered and dried in the vacuum oven at 50° C. for 12 hours to give 121.8 g (73%) of 1-(5-bromo-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)-3-ethylurea as an off-white solid.

Workup

  1. customwas prepared
  2. stirringThis mixture was stirred at room temperature for 6 hours
  3. filtrationThe solid was collected by filtration
  4. washrinsed with tetrahydrofuran (2×500 mL)
  5. concentrationThe combined tetrahydrofuran layers were concentrated to a viscous, yellow semi-solid which
  6. washwas then washed with water (2×500 mL)
  7. stirringThis solid was further stirred with water (500 mL) for 18 hours
  8. filtrationfiltered
  9. customdried in the vacuum oven at 50° C. for 12 hours

Sources & evidence

ORD record
ord-711f7d3b62c14d9d8035dd9bbc193e39
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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