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

HRID 2279614ノート

反応式

HRID 2279614 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0739416e271d4c98a733b8d9c94f6cfb
出典データセット
uspto-grants-2015_09
特許番号
US09133204B2

反応ノート

読み込み中…