4-Fluorobenzylamine → HCID 24956129, compound

HRID 1879180Notes

Reaction equation

HRID 1879180 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[CH:14]=[CH:13][C:12]([C:15]3[S:16][C:17]([C:21]([OH:23])=O)=[C:18]([CH3:20])[N:19]=3)=[N:11]2)=[CH:4][CH:3]=1.[F:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][NH2:30])=[CH:27][CH:26]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[F:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][NH:30][C:21]([C:17]2[S:16][C:15]([C:12]3[CH:13]=[CH:14][N:10]([CH2:9][CH2:8][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[N:11]=3)=[N:19][C:18]=2[CH3:20])=[O:23])=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 673264-FluorobenzylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68490567HCID 68490567, compound

Product 1

HCID 24956129HCID 24956129, compoundYield 63.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-{1-[2-(4-fluoro-phenyl)-ethyl]-1H-pyrazol-3-yl}-4-methyl-thiazole-5-carboxylic acid (0.1 g, 0.30 mmol) in methylene chloride (5 mL) was added 4-fluoro benzyl amine (0.04 g, 0.33 mmol), benzotriazol-1-yloxytris-(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 0.146 g, 0.33 mmol) and N,N-diisopropylethylamine (0.1 mL, 0.60 mmol) and the mixture was stirred under nitrogen at room temperature for 16 hr. The reaction mixture was diluted with methylene chloride (50 mL), washed with water (50 mL) and brine (2×50 mL). The organic phase was dried (Na2SO4) and evaporated. The residue was purified by preparative thin layer chromatography over silica gel (hexanes:ethyl acetate, 1:1) to provide 2-{1-[2-(4-fluoro-phenyl)-ethyl]-1H-pyrazol-3-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (83 mg, 62% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.30 (m, 2H), 7.14 (d, J=4.0 Hz, 1H), 6.92-7.07 (m, 6H), 6.72 (d, J=4.0 Hz, 1H), 6.06 (bs, 1H), 4.58 (d, J=4.0 Hz, 2H), 4.34 (t, J=8.0 Hz, 2H), 3.16 (t, J=8.0 Hz, 2H), 2.75 (s, 3H); MS (M+H)+=439.1; Rt=1.55 min; HRMS (M+H)+=439.14.

Workup

  1. washwashed with water (50 mL) and brine (2×50 mL)
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. customevaporated
  4. customThe residue was purified by preparative thin layer chromatography over silica gel (hexanes:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-7309fca8b2c445d9851b4063b3ad1108
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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