3-Amino-1,2-propanediol → 3-(3-tert-butyl-5-{[({2-fluoro-4-[(2-methylpyridin-4-yl)oxy]phenyl}amino)carbonyl]-amino}-1H-pyrazol-1-yl)-N-(2,3-dihydroxypropyl)benzamide

HRID 221908Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 221908
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([CH3:27])[CH:22]=3)=[CH:16][C:15]=2[F:28])=[O:12])[N:7]([C:29]2[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=2)[C:32](O)=[O:33])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:38][CH2:39][CH:40]([OH:43])[CH2:41][OH:42].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C1C=CN=CC=1.C1COCC1.C(Cl)Cl.O.C(OCC)(=O)C>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([CH3:27])[CH:22]=3)=[CH:16][C:15]=2[F:28])=[O:12])[N:7]([C:29]2[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=2)[C:32]([NH:38][CH2:39][CH:40]([OH:43])[CH2:41][OH:42])=[O:33])[N:6]=1)([CH3:2])([CH3:4])[CH3:3]

Komponenten

10

Edukt 4

HCID 735613-Amino-1,2-propanediolHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 536301863-(3-Tert-butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-benzoic acid

Produkt 1

HCID 116927143-(3-tert-butyl-5-{[({2-fluoro-4-[(2-methylpyridin-4-yl)oxy]phenyl}amino)carbonyl]-amino}-1H-pyrazol-1-yl)-N-(2,3-dihydroxypropyl)benzamideAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 3-(3-tert-butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-benzoic acid (100 mg, 0.20 mmol), 3-aminopropane-1,2-diol (22 mg, 0.24 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (46 mg, 0.24 mmol), 4-dimethylaminopyridine (29 mg, 0.24 mmol) and 1-hydroxybenzotriazole (32 mg, 0.24 mmol) in THF and DCM was stirred at room temperature overnight. Ethyl acetate and water were added, and the organic phase was washed with brine, dried over MgSO4, and evaporated at reduced pressure. HPLC purification (10-90% aqueous acetonitrile) afforded pure title compound (23 mg, 20%). 1H-NMR (DMSO-d6) δ 8.97 (s, 1H), 8.91 (s, 1H), 8.55 (t, J=5.7 Hz, 1H), 8.29 (d, J=7.2 Hz, 1H), 8.11 (t, J=9.0 Hz, 1H), 7.98 (s, 1H), 7.89 (d, J=7.2 Hz, 1H), 7.64-7.58 (m, 2H), 7.18 (d, J=9.0 Hz, 1H), 6.94 (d, J=12.0 Hz, 1H), 6.76 (s, 1H), 4.81 (s, 1H), 4.57 (s, 1H), 3.62 (t, J=5.7 Hz, 1H). 3.40 (m, 2H), 3.18 (m, 2H), 2.36 (s, 3H), 1.80 (s, 9H); MS LC-MS [M+H]+=577.3, RT=1.54 min.

Aufarbeitung

  1. washthe organic phase was washed with brine
  2. dry with materialdried over MgSO4
  3. customevaporated at reduced pressure
  4. customHPLC purification (10-90% aqueous acetonitrile)

Quellen und Nachweise

ORD-Eintrag
ord-8e63b27600ba4efe9c684cc9aadcf640
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08207166B2

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