Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 178432530、化合物

HRID 1621434ノート

反応式

HRID 1621434 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:24]2[N:32]=[C:31]([CH3:33])[N:30]=[C:29]3[C:25]=2[N:26]=[CH:27][N:28]3C2CCCCO2)[C:5]([NH:8][C:9]2[C:10]3[CH:11]=[N:12][N:13](C4CCCCO4)[C:14]=3[CH:15]=[CH:16][CH:17]=2)=[N:6][CH:7]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:24]2[N:32]=[C:31]([CH3:33])[N:30]=[C:29]3[C:25]=2[N:26]=[CH:27][NH:28]3)[C:5]([NH:8][C:9]2[C:10]3[CH:11]=[N:12][NH:13][C:14]=3[CH:15]=[CH:16][CH:17]=2)=[N:6][CH:7]=1

参加物

4

反応物 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-2 回HCID 59548169N-(5-chloro-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine

生成物 1

HCID 178432530HCID 178432530、化合物収率 82%

試薬・触媒・溶媒 1

HCID 21226129Dichloromethane methanol溶媒

反応条件

温度
40 °C

実験手順

A solution of N-(5-chloro-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine (96.8 mg, 178 μmol) in DCM/MeOH (4.0 mL, 1:1) was treated with (+/−)-10-camphorsulfonic acid (91 mg, 391 μmol) and the stirred mixture placed in an oil bath at 40° C. The heater was turned off and the mixture stirred for 16 h. LCMS showed predominantly monodeprotection, so an additional 90 mg of CSA was added (4.4 equiv. total). The mixture was heated at 40° C. until LCMS indicated complete deprotection. The mixture was cooled and purified by ion exchange chromatography (washing with MeOH, eluting off with 2N NH3/MeOH). The product was concentrated, taken up in MeOH (3 mL), sonicated and allowed to stand. N-(5-Chloro-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indazol-4-amine (55 mg, 82% yield) crystallized out and was collected by filtration as an orange solid. 1H NMR of free base thus obtained gives broad signals, so a small amount was converted to the HCl salt for better 1H NMR analysis by dissolving in MeOH containing 2 drops 2 M aqueous HCl followed by concentration to dryness. HCl salt: 1H NMR (400 MHz, d6-DMSO) δ 11.29 (br. s., 1H); 10.17 (br. s., 1H); 10.04 (s, 1H); 9.27 (d, J=2.69 Hz, 1H); 8.93 (s, 1H); 8.40 (s, 1H); 8.30 (d, J=2.69 Hz, 1H); 7.89 (d, J=9.54 Hz, 1H); 7.52 (d, J=9.54 Hz, 1H); 2.15 (s, 3H). m/z (ESI, +ve) 377.0 (M+H)+.

後処理

  1. customthe stirred mixture placed in an oil bath at 40° C
  2. temperatureThe mixture was cooled
  3. custompurified by ion exchange chromatography (washing with MeOH, eluting off with 2N NH3/MeOH)
  4. concentrationThe product was concentrated
  5. customsonicated

出典と根拠

ORDレコード
ord-c74b02d881e64039b9c0b2b8b5942bc6
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

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