Triethylamine → 2-(4-bromobutanamido)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

HRID 883134Notes

Reaction equation

HRID 883134 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[O:9])=[C:5]([CH3:7])[N:6]=1.C(N(CC)CC)C.[Br:26][CH2:27][CH2:28][CH2:29][C:30](Cl)=[O:31]>O1CCCC1.ClCCl>[Br:26][CH2:27][CH2:28][CH2:29][C:30]([NH:1][C:2]1[S:3][C:4]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[O:9])=[C:5]([CH3:7])[N:6]=1)=[O:31]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 702254-Bromobutyryl chlorideHCID 551152032-amino-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

Product 1

HCID 866387312-(4-bromobutanamido)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamideYield 92%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-amino-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide (5.60 g, 22.0 mmol) and triethylamine (2.61 g, 26.0 mmol) in anhydrous tetrahydrofuran (250 mL) was added 4-bromobutanoyl chloride (4.99 g, 26.0 mmol) in anhydrous dichloromethane (10 mL) dropwise at 0° C. The reaction mixture was stirred at ambient temperature for 2 hours, then diluted with dichloromethane (200 mL) and washed with saturated aqueous sodium bicarbonate solution (2×150 mL), and brine (150 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrate in vacuo to afford the title compound as a yellow oil in 92% yield (8.00 g): 1H NMR (300 MHz, CDCl3) δ 8.61 (br s, 1H), 7.32-7.22 (m, 2H), 7.05-6.94 (m, 2H), 6.14 (t, J=5.6 Hz, 1H), 4.53 (d, J=5.6 Hz, 2H), 3.45 (t, J=6.7 Hz, 2H), 2.65 (t, J=6.7 Hz, 2H), 2.58 (s, 3H), 2.23 (quintet, J=6.7 Hz, 2H); MS (ES+) m/z 413.1 (M+1), 415.1 (M+1).

Workup

  1. washwashed with saturated aqueous sodium bicarbonate solution (2×150 mL), and brine (150 mL)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrate in vacuo

Sources & evidence

ORD record
ord-dc3e4df21bec4968b856c0251f7bd969
Source dataset
uspto-grants-2012_08
Patent number
US08236835B2

Reaction notes

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