Triethylamine → 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-N-((5-fluoropyridin-3-yl)methyl)-4-methylthiazole-5-carboxamide

HRID 1882451Notes

Reaction equation

HRID 1882451 reaction equation
[CH:1]1([CH2:4][N:5]2[CH2:9][CH2:8][N:7]([C:10]3[S:11][C:12]([C:16]([OH:18])=O)=[C:13]([CH3:15])[N:14]=3)[C:6]2=[O:19])[CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C.[F:51][C:52]1[CH:53]=[C:54]([CH2:58][NH2:59])[CH:55]=[N:56][CH:57]=1>CN(C)C=O.C(OCC)(=O)C>[CH:1]1([CH2:4][N:5]2[CH2:9][CH2:8][N:7]([C:10]3[S:11][C:12]([C:16]([NH:59][CH2:58][C:54]4[CH:55]=[N:56][CH:57]=[C:52]([F:51])[CH:53]=4)=[O:18])=[C:13]([CH3:15])[N:14]=3)[C:6]2=[O:19])[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45116207(5-Fluoropyridin-3-yl)methanamineHCID 579198202-(3-(Cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid

Product 1

HCID 579200012-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-N-((5-fluoropyridin-3-yl)methyl)-4-methylthiazole-5-carboxamideYield 47%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid (1.00 g, 3.55 mmol), 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 1.70 g, 4.47 mmol) and triethylamine (1.00 mL, 7.17 mmol) in N,N-dimethylformamide (15 mL) was added (5-fluoropyridin-3-yl)methanamine (0.55 g, 4.36 mmol). The reaction mixture was stirred at ambient temperature for 20 h, diluted with ethyl acetate (200 mL) and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was recrystallized from ethyl acetate to afford the title compound as a white powder in 47% yield (0.65 g): mp 144-145° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.53 (J=6.0 Hz, 1H), 8.43-8.38 (m, 2H), 7.59-7.56 (m, 1H), 4.39 (d, J=6.0 Hz, 2H), 4.00-3.95 (m, 2H), 3.64-3.59 (m, 2H), 3.06 (d, J=6.0 Hz, 2H), 2.44 (s, 3H), 0.95-0.87 (m, 1H), 0.48-0.42 (m, 2H), 0.20-0.16 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 162.4, 161.1, 157.9, 155.2, 145.5, 137.9, 136.6, 122.5, 122.3, 117.6, 48.2, 42.5, 42.3, 40.8, 17.6, 9.3, 3.6; MS (ES+) m/z 389.9 (M+1).

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-3372e1a5c81e4dc49bd178b70144070f
Source dataset
uspto-grants-2012_11
Patent number
US08318949B2

Reaction notes

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