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 221908

반응식

HRID 221908 반응식
[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]

참가 물질

10

반응물 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

생성물 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)benzamide수율 20%

시약·촉매·용매 5

HCID 142844-(Dimethylamino)pyridine촉매HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-8e63b27600ba4efe9c684cc9aadcf640
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08207166B2

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