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

HRID 2279614노트

반응식

HRID 2279614 반응식
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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0739416e271d4c98a733b8d9c94f6cfb
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133204B2

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