Diisopropylethylamine → 1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-methylpyrrolidine-2-carboxamide

HRID 1485309ノート

反応式

HRID 1485309 の反応式
[CH:1]([C:4]1[NH:8][N:7]=[C:6]([NH:9][C:10]2[C:11]3[CH2:26][CH2:25][CH2:24][C:12]=3[N:13]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH:17]3[C:21](O)=[O:22])[N:15]=2)[CH:5]=1)([CH3:3])[CH3:2].Cl.CN.[CH3:30][N:31](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[CH:1]([C:4]1[NH:8][N:7]=[C:6]([NH:9][C:10]2[C:11]3[CH2:26][CH2:25][CH2:24][C:12]=3[N:13]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH:17]3[C:21]([NH:31][CH3:30])=[O:22])[N:15]=2)[CH:5]=1)([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867236291-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylic acid

生成物 1

HCID 762842451-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-methylpyrrolidine-2-carboxamide収率 6.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylic acid (300 mg, 0.842 mmol) in DMF (5 mL) was added methylamine hydrochloride (284 mg, 4.207 mmol), HATU (320 mg, 0.842 mmol), diisopropylethylamine (163 mg, 1.263 mmol). The reaction mixture was stirred at RT for 16 h. The progress of reaction was monitored by LCMS. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (3×30 mL). The organic layer was washed with water (8×40 mL) and dried over anhydrous sodium sulfate. Removal of solvent under vacuum gave a crude product which was purified by reverse HPLC to obtain pure 1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-methylpyrrolidine-2-carboxamide (20 mg) as racemate. The enantiomers were separated by chiral HPLC to afford (R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-methylpyrrolidine-2-carboxamide (5 mg). 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 1.30 (d, 6H), 1.95-2.25 (m, 6H), 2.68 (s, 3H), 2.74 (t, 2H), 2.78 (t, 2H), 2.93-3.03 (m, 1H), 3.59 (brs, 1H), 3.80 (brs, 1H), 4.54 (d, 1H), 6.40 (brs, 1H). The other enantiomer was made using the chiral (R) starting material.

後処理

  1. customThe progress of reaction
  2. extractionextracted with EtOAc (3×30 mL)
  3. washThe organic layer was washed with water (8×40 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customRemoval of solvent under vacuum
  6. customgave a crude product which
  7. customwas purified by reverse HPLC

出典と根拠

ORDレコード
ord-cf6de051d0eb4beb8d517d9939251360
出典データセット
uspto-grants-2016_08
特許番号
US09422267B2

反応ノート

読み込み中…