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

HRID 1410019Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1410019
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

Komponenten

6

Edukt 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

Produkt 1

HCID 665517406-amino-N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)nicotinamideAusbeute 33,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-eb50e726a23e4967b35c23d026a39d5a
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921383B2

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