1-Hydroxybenzotriazole → 3-(3-tert-Butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-N-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-benzamide

HRID 1174878노트

반응식

HRID 1174878 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]([OH:34])=O)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:38][C:39]1([CH3:46])[O:43][CH:42]([CH2:44][NH2:45])[CH2:41][O:40]1.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:45][CH2:44][CH:42]2[CH2:41][O:40][C:39]([CH3:46])([CH3:38])[O:43]2)=[O:34])[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

10

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 41223491,3-Dioxolane-4-methanamine, 2,2-dimethyl-HCID 536301863-(3-Tert-butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-benzoic acid

생성물 1

HCID 115345853-(3-tert-Butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-N-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-benzamide수율 73%

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 (300.0 mg, 0.60 mmol), 1-(2,2-dimethyl-1,3-dioxolan-4-yl)methanamine (93.8 mg, 0.71 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (136.6 mg, 0.71 mmol), 4-dimethylaminopyridine (87.3 mg, 0.71 mmol) and 1-hydroxybenzotriazole (96.6 mg, 0.71 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 (270 mg, 73%). 1H-NMR (DMSO-d6) δ 8.93 (s, 1H), 8.88 (s, 1H), 8.72 (t, J=6.07.66 (m, 2H), 8.30 (d, J=5.7 Hz), 8.13 (t, J=9.0 Hz, 1H), 7.98 (s, 1H), 7.89 (d, J=9.0 Hz, 1H), 7.69 (m, 2H), 7.19 (d, J=14.7 Hz, 1H), 6.96 (d, J=10.2 Hz, 1H), 6.76 (s, 1H), 6.72 (d, J=5.7 Hz, 1H), 6.41 (s, 1H), 3.95 (t, J=6.3 Hz, 1H), 3.68 (t, J=6.0 Hz, 1H) 3.28-3.45 (m, 2H), 1.314 (s, 3H), 1.27 (s, 9H), 1.22 (s, 3H); MS LC-MS [M+H]+=617.3, RT=2.54 min.

후처리

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

출처 및 근거

ORD 기록
ord-77d719f4f56c4ba49cc9b8370f5a82a5
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07838524B2

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