Hydrochloric Acid → N-{2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl]-5-methoxy-6-(pyridin-4-ylamino)pyrimidin-4-yl}-2-methoxyacetamide

HRID 1482931ノート

反応式

HRID 1482931 の反応式
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]3[CH2:23][CH2:22][CH2:21][C:10]=3[N:11]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])[N:12]=2)[N:5]=[C:4]([NH:24][C:25](=[O:29])[CH2:26][O:27][CH3:28])[C:3]=1[O:30][CH3:31].Cl.Br[C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C=O)C.O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[F:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH2:13][N:11]1[C:10]2[CH2:21][CH2:22][CH2:23][C:9]=2[C:8]([C:6]2[N:5]=[C:4]([NH:24][C:25](=[O:29])[CH2:26][O:27][CH3:28])[C:3]([O:30][CH3:31])=[C:2]([NH:1][C:34]3[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=3)[N:7]=2)=[N:12]1

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 881004-Bromopyridinium chlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 90015879N-{6-amino-2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazol-3-yl]-5-methoxypyrimidin-4-yl}-2-methoxyacetamide

生成物 1

HCID 72202406N-{2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl]-5-methoxy-6-(pyridin-4-ylamino)pyrimidin-4-yl}-2-methoxyacetamide

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
105 °C

実験手順

50 mg of N-{6-amino-2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazol-3-yl]-5-methoxypyrimidin-4-yl}-2-methoxyacetamide 1-7-1 (0.12 mmol, 1.00 eq.), 25 mg of 4-bromopyridine hydrochloride (1:1) (0.13 mmol, 1.10 eq.), mg of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.02 mmol, 0.15 eq.), 115 mg of caesium carbonate (0.36 mmol, 3.00 eq.) and 2.6 mg of palladium diacetate (0.012 mmol, 0.1 eq.) were suspended in 0.5 mL of dry DMF and stirred under nitrogen atmosphere at 105° C. bath temperature for two h. The reaction mixture was diluted with water, the pH was adjusted to 7.5 using 4N aqueous hydrochloric acid and the crude product was extracted with DCM. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography yielding 29 mg (0.06 mmol, 49%) of analytically pure target compound.

後処理

  1. extractionthe crude product was extracted with DCM
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography
  5. customyielding 29 mg (0.06 mmol, 49%) of analytically pure target compound

出典と根拠

ORDレコード
ord-21409567c7e1445694d895a847b23b7a
出典データセット
uspto-grants-2016_08
特許番号
US09416125B2

反応ノート

読み込み中…