1-Methylimidazole → 6-amino-N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)nicotinamide

HRID 1410019ノート

反応式

HRID 1410019 の反応式
Cl.[NH2:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH3:27])[CH:19]=3)[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=2)[CH2:4]1.[NH2:28][C:29]1[CH:37]=[CH:36][C:32]([C:33](O)=[O:34])=[CH:31][N:30]=1.CCN=C=NCCCN(C)C.CN1C=CN=C1>C(Cl)Cl>[NH2:28][C:29]1[CH:37]=[CH:36][C:32]([C:33]([NH:2][CH:3]2[CH2:7][CH2:6][N:5]([C:8]3[N:9]=[C:10]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH3:27])[CH:19]=4)[C:11]4[N:16]=[CH:15][S:14][C:12]=4[N:13]=3)[CH2:4]2)=[O:34])=[CH:31][N:30]=1

参加物

6

反応物 4

HCID 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 184966-Aminonicotinic acidHCID 683792715-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride

生成物 1

HCID 665517406-amino-N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)nicotinamide収率 33.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of 5-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride (100 mg, 0.245 mmol), 6-aminonicotinic acid (40 mg, 0.27 mmol), EDCI (97 mg, 0.49 mmol) and N-methylimidazole (60 mg, 0.735 mmol) in 5 mL of DCM was stirred at room temperature for 16 hours. The mixture was washed with water (5 mL), The organic layer was dried over Na2SO4. After filtration and concentration, the residue was purified by column chromatography on silica gel eluting with a mixture of CH2Cl2 and methanol (100:1→15:1) to give 6-amino-N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)nicotinamide (40 mg, 33%). 1H NMR (300 MHz, DMSO): δ 9.57 (s, 1H), 8.81 (s, 1H), 8.475-8.46 (m, 1H), 8.27-8.25 (m, 2H), 7.60-7.25 (m, 2H), 6.92 (d, 1H, J=8.7 Hz), 6.47-6.39 (m, 3H), 4.54-4.52 (m, 1H), 3.76-3.58 (m, 10H), 2.34-2.04 (m, 2H). LC-MS: 247 [M/2+H]+, 493 [M+H]+, 491 [M−H]−, tR=1.22 min. HPLC: 95.20% at 214 nm, 95.06% at 254 nm, tR=5.64 min.

後処理

  1. washThe mixture was washed with water (5 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationAfter filtration and concentration
  4. customthe residue was purified by column chromatography on silica gel eluting with a mixture of CH2Cl2 and methanol (100:1→15:1)

出典と根拠

ORDレコード
ord-eb50e726a23e4967b35c23d026a39d5a
出典データセット
uspto-grants-2014_12
特許番号
US08921383B2

反応ノート

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