Water → 5-[8-[(6-chloroquinolin-4-yl)methyl]-6-(cyclopropylmethyl)-3-methyl-5-oxo-6,8-dihydro-5H-imidazo[1,2-c]pyrazolo[4,3-e]pyrimidin-9-yl]-1-methyl-1H-pyrrole-3-carbonitrile

HRID 2222237ノート

反応式

HRID 2222237 の反応式
[NH2:1][C:2]1[C:3]2[C:4](=[N:13][N:14]([CH2:24][C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[C:32]([Cl:35])[CH:33]=4)[N:28]=[CH:27][CH:26]=3)[C:15]=2[C:16]2[N:20]([CH3:21])[CH:19]=[C:18]([C:22]#[N:23])[CH:17]=2)[N:5]([CH2:9][CH:10]2[CH2:12][CH2:11]2)[C:6](=[O:8])[N:7]=1.[CH2:36]1[CH2:46]CN2C(=NCCC2)C[CH2:37]1.ClCC(=O)C.O>CN(C=O)C.C(OCC)(=O)C>[Cl:35][C:32]1[CH:33]=[C:34]2[C:29](=[CH:30][CH:31]=1)[N:28]=[CH:27][CH:26]=[C:25]2[CH2:24][N:14]1[C:15]([C:16]2[N:20]([CH3:21])[CH:19]=[C:18]([C:22]#[N:23])[CH:17]=2)=[C:3]2[C:2]3[N:7]([C:36]([CH3:46])=[CH:37][N:1]=3)[C:6](=[O:8])[N:5]([CH2:9][CH:10]3[CH2:12][CH2:11]3)[C:4]2=[N:13]1

参加物

7

反応物 4

HCID 962WaterHCID 6571Chloroacetone2 回HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 104354585-[4-amino-2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-6-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyrimidin-3-yl]-1-methyl-1H-pyrrole-3-carbonitrile

生成物 1

HCID 115554615-[8-[(6-chloroquinolin-4-yl)methyl]-6-(cyclopropylmethyl)-3-methyl-5-oxo-6,8-dihydro-5H-imidazo[1,2-c]pyrazolo[4,3-e]pyrimidin-9-yl]-1-methyl-1H-pyrrole-3-carbonitrile収率 25.5%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
125 °C

実験手順

5-[4-amino-2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-6-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyrimidin-3-yl]-1-methyl-1H-pyrrole-3-carbonitrile (75 mg, 0.15 mmol) was dissolved in 1.5 mL anhydrous DMF with 30 mg DBU. Chloroacetone (28 mg, 0.3 mmol, 2.0 eq.) was added and the resulting solution heated in the microwave for 90 minutes at 125° C. Two addition eq. chloroacetone were added, and the reaction returned to the microwave and heated an additional 90 minutes at 125° C. The reaction mixture was diluted with 50 mL. water and 50 mL ethyl acetate. The aqueous layer was washed 3×50 mL with ethyl acetate. The combined organic fractions were washed with 50 mL brine and dried over sodium sulfate. The crude product was purified by chromatography on silica (gradient: dichloromethane to 10% methanol in dichloromethane), followed by reverse phase HPLC using 40% aqueous acetonitrile, yielding 20 mg product. 1H NMR (300 MHz, CHLOROFORM-D) d ppm 0.55 (m, 4H) 1.48 (m, 1H) 2.27 (d, J=0.94 Hz, 3H) 3.42 (s, 3 H) 4.13 (m, 2H) 5.82 (m, 2H) 6.62 (dd, J=4.52, 1.88 Hz, 1H) 6.76 (d, J=4.33 Hz, 1H) 7.36 (d, J=1.51 Hz, 1H) 7.44 (d, J=1.13 Hz, 1H) 7.70 (dd, J=9.04, 2.26 Hz, 1H) 7.90 (d, J=2.26 Hz, 1H) 8.10 (m, 1H) 8.81 (d, J=4.52 Hz, 1H); ES M+H+=524.

後処理

  1. additionwere added
  2. temperatureheated an additional 90 minutes at 125° C
  3. additionThe reaction mixture was diluted with 50 mL
  4. washThe aqueous layer was washed 3×50 mL with ethyl acetate
  5. washThe combined organic fractions were washed with 50 mL brine
  6. dry with materialdried over sodium sulfate
  7. customThe crude product was purified by chromatography on silica (gradient: dichloromethane to 10% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-d3bbd59f98b044f18f86ba0e19566214
出典データセット
uspto-grants-2008_05
特許番号
US07371757B2

反応ノート

読み込み中…