Triethylamine → 2,4-Diamino-6-((1-(1-methyl-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrile

HRID 75343ノート

反応式

HRID 75343 の反応式
[CH3:1][N:2]1[C:10]2[C:5](=[N:6][C:7]([CH:18]([NH2:20])[CH3:19])=[C:8]([N:11]3[CH2:17][C:13]4([CH2:16][O:15][CH2:14]4)[CH2:12]3)[CH:9]=2)[CH:4]=[CH:3]1.[NH2:21][C:22]1[N:27]=[C:26]([NH2:28])[C:25]([C:29]#[N:30])=[C:24](Cl)[N:23]=1.CCN(CC)CC>CN(C=O)C.CCOC(C)=O>[NH2:21][C:22]1[N:27]=[C:26]([NH2:28])[C:25]([C:29]#[N:30])=[C:24]([NH:20][CH:18]([C:7]2[N:6]=[C:5]3[CH:4]=[CH:3][N:2]([CH3:1])[C:10]3=[CH:9][C:8]=2[N:11]2[CH2:17][C:13]3([CH2:16][O:15][CH2:14]3)[CH2:12]2)[CH3:19])[N:23]=1

参加物

6

反応物 3

HCID 8471TriethylamineHCID 867080131-(1-Methyl-6-(2-oxa-6-azaspiro[3,3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamineHCID 867080212,4-Diamino-6-chloropyrimidine-5-carbonitrile

生成物 1

HCID 730560002,4-Diamino-6-((1-(1-methyl-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrile

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

To a 10 mL vial were added 1-(1-methyl-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (81 mg, 0.30 mmol), 2,4-diamino-6-chloropyrimidine-5-carbonitrile (50.4 mg, 0.297 mmol) and Et3N (0.083 mL, 0.60 mmol) in DMF (2 mL). The resulting yellow solution was heated to 90° C. and stirred for 5 hours. The reaction mixture was diluted with EtOAc and washed with saturated NH4Cl (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The desired compound was precipitated with ether, filtered, and purified by silica gel column chromatography, eluting with 1:1 EtOAc/hexane to 100% EtOAc to 9:1 EtOAc/MeOH gradient. The resulting yellow foam was further purified by preparative HPLC eluting with 20-40% ACN in water (with 0.05% ammonium bicarbonate). The fractions containing the product were combined and lyophilized to give the title compounds (racemate) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.28-1.40 (m, 3 H), 3.71-3.82 (m, 3 H), 3.96-4.07 (m, 2 H), 4.14-4.25 (m, 2 H), 4.72-4.85 (m, 4 H), 5.44-5.58 (m, 1 H), 6.37-6.45 (m, 1 H), 6.45-6.55 (m, 2H), 6.55-6.66 (m, 2 H), 6.68-6.79 (m, 1 H), 7.08-7.16 (m, 1 H), 7.37-7.45 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C20H23N9O, 406.2; found 406.5.

後処理

  1. washwashed with saturated NH4Cl (3×)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe desired compound was precipitated with ether
  6. filtrationfiltered
  7. custompurified by silica gel column chromatography
  8. washeluting with 1:1 EtOAc/hexane to 100% EtOAc to 9:1 EtOAc/MeOH gradient
  9. customThe resulting yellow foam was further purified by preparative HPLC
  10. washeluting with 20-40% ACN in water (with 0.05% ammonium bicarbonate)
  11. additionThe fractions containing the product

出典と根拠

ORDレコード
ord-86ee6b270e7a423fa6cdbe175ac798e7
出典データセット
uspto-grants-2014_09
特許番号
US08835420B2

反応ノート

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