1-(Methylamino)adamantane → 3-(Difluoromethyl)-1-(5-fluoro-pyrimidin-2-yl)-1h-pyrazole-4-carboxylic acid (adamantan-1-ylmethyl)-amide

HRID 2279614Notes

Reaction equation

HRID 2279614 reaction equation
F[P-](F)(F)(F)(F)F.[N:8]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:12]2C=CC=CC=2N=N1.[F:28][CH:29]([F:45])[C:30]1[C:34]([C:35]([OH:37])=O)=[CH:33][N:32]([C:38]2[N:43]=[CH:42][C:41]([F:44])=[CH:40][N:39]=2)[N:31]=1.[C:46]12(NC)[CH2:55][CH:50]3[CH2:51][CH:52]([CH2:54][CH:48]([CH2:49]3)[CH2:47]1)[CH2:53]2.CC(N(C)C)=O>CN(C=O)C>[C:46]12([CH2:12][NH:8][C:35]([C:34]3[C:30]([CH:29]([F:28])[F:45])=[N:31][N:32]([C:38]4[N:43]=[CH:42][C:41]([F:44])=[CH:40][N:39]=4)[CH:33]=3)=[O:37])[CH2:47][CH:48]3[CH2:49][CH:50]([CH2:51][CH:52]([CH2:54]3)[CH2:53]1)[CH2:55]2

Participants

6

Reactant 4

HCID 194761-(Methylamino)adamantaneHCID 31374DimethylacetamideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 595798213-(Difluoromethyl)-1-(5-fluoropyrimidin-2-yl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 595798793-(Difluoromethyl)-1-(5-fluoro-pyrimidin-2-yl)-1h-pyrazole-4-carboxylic acid (adamantan-1-ylmethyl)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

BOP (98 mg, 0.22 mmol) is added to a solution of 3-(difluoromethyl)-1-(5-fluoropyrimidin-2-yl)-1H-pyrazole-4-carboxylic acid (38 mg, 0.147 mmol), admantan-1-yl-methylamine (24 mg, 0.147 mmol) and DMA (0.052 mL) in DMF (1.0 mL) at rt. The mixture is stirred for 20 h. The mixture is poured into ice water (5 mL), extracted with EtOAc (3×20 mL) and dried over anhydrous MgSO4. The crude product is purified by silica gel column chromatography using 30% EtOAc/hexane to afford the title compound as a white solid. 1H NMR (DMSO-D6): 9.45 (s, 1H), 9.05 (s, 2H), 8.35 (m, 1H), 7.29-7.36 (t, 1H), 2.93 (d, 2H), 1.91 (m, 3H), 1.47-1.65 (m, 12H). MS (M+1)=406.28; RT=1.34 min *IC50.

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialdried over anhydrous MgSO4
  3. customThe crude product is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0739416e271d4c98a733b8d9c94f6cfb
Source dataset
uspto-grants-2015_09
Patent number
US09133204B2

Reaction notes

Loading…