Triethylamine → tert-Butyl (S)-4-(5-(1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-1,4-diazepane-1-carboxylate

HRID 2205596ノート

反応式

HRID 2205596 の反応式
[NH2:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]#[N:10])=[C:4]([CH3:11])[N:3]=1.[NH2:12][C@H:13]([C:15]1[N:20]=[C:19]2[CH:21]=[CH:22][N:23]([CH3:24])[C:18]2=[CH:17][C:16]=1[N:25]1[CH2:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27][CH2:26]1)[CH3:14].C(N(CC)CC)C>CS(C)=O>[NH2:1][C:2]1[N:7]=[C:6]([NH:12][C@H:13]([C:15]2[N:20]=[C:19]3[CH:21]=[CH:22][N:23]([CH3:24])[C:18]3=[CH:17][C:16]=2[N:25]2[CH2:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:27][CH2:26]2)[CH3:14])[C:5]([C:9]#[N:10])=[C:4]([CH3:11])[N:3]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 754124462-Amino-4-chloro-6-methyl-5-pyrimidinecarbonitrileHCID 118214737tert-Butyl (S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-1,4-diazepane-1-carboxylate

生成物 1

HCID 118214740tert-Butyl (S)-4-(5-(1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-1,4-diazepane-1-carboxylate収率 69.7%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
90 °C

実験手順

To a 25 mL pear flask were added 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (70.7 mg, 0.419 mmol) and tert-butyl (S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-1,4-diazepane-1-carboxylate (87 mg, 0.23 mmol) in DMSO (1.2 mL). Triethylamine (162 μL, 1.17 mmol) was added to the mixture which was then heated to 90° C. After 1 hour, UPLC indicated the reaction was complete. The reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over MgSO4, filtered, and concentrated. The residue was purified by liquid chromatography (SiO2, 25-100% EtOAc/heptanes gradient) to give the title compound as a foam (81 mg, 69%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.35-1.52 (m, 12H), 1.91 (s, 2H), 2.24 (s, 3H), 2.95-3.19 (m, 4H), 3.57 (d, J=5.56 Hz, 4H), 3.80 (br s, 1H), 5.90-6.01 (m, 1H), 6.49 (d, J=3.28 Hz, 1H), 6.95 (br s, 4H), 7.55 (d, J=3.03 Hz, 1H), 7.81 (d, J=6.82 Hz, 1H); ESI-MS m/z [M+H]+ calc'd for C26H35N9O2, 506. found 506.

後処理

  1. customThe reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by liquid chromatography (SiO2, 25-100% EtOAc/heptanes gradient)

出典と根拠

ORDレコード
ord-caff64cf3021439f87ab039a5c86f978
出典データセット
uspto-grants-2016_06
特許番号
US09371321B2

反応ノート

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