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1-Hydroxybenzotriazole → methyl 4-[4,4-difluoro-1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinylmethoxy]benzoate

HRID 350500
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HRID 350500 반응식
[F:1][C:2]1([F:19])[CH2:6][NH:5][CH:4]([CH2:7][O:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)[CH2:3]1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH2:39][C:40](O)=[O:41])[CH:25]=[CH:26][C:27]=1[NH:28][C:29]([NH:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[CH3:38])=[O:30].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C1C=CN=CC=1)C.CN(C=O)C.CCOC(C)=O>[F:19][C:2]1([F:1])[CH2:6][N:5]([C:40](=[O:41])[CH2:39][C:24]2[CH:25]=[CH:26][C:27]([NH:28][C:29]([NH:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[CH3:38])=[O:30])=[C:22]([O:21][CH3:20])[CH:23]=2)[CH:4]([CH2:7][O:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)[CH2:3]1
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참가 물질

8

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 114498403-Methoxy-4-o-tolylureidophenylacetic acidHCID 23512388Methyl 4-(4,4-difluoro-2-pyrrolidinylmethoxy)benzoate

생성물 1

HCID 69332941methyl 4-[4,4-difluoro-1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinylmethoxy]benzoate
수율 89%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of methyl 4-(4,4 difluoro-2-pyrrolidinylmethoxy)benzoate (540 mg, 1.99 mmol), 3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetic acid (626 mg, 1.99 mmol), EDC.HCl (572 mg, 2.99 mmol), HOBt (cat.), and DMAP (cat.) in DMF (10 ml) was stirred overnight. The mixture was diluted with EtOAc (300 ml), washed with brine (2×100 ml), dried over MgSO4, and concntrated in vacuo. The residue was chromatographed on silica gel with CHCl3-MeOH (20:1) as eluent to give methyl 4-[4,4-difluoro-1-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinylmethoxy]benzoate (1.00 g, 89%) as a colorless foam. 1H-NMR (CDCl3) δ 2.31 (s, 3 H), 2.47–2.63 (m, 2 H), 3.52–3.97 (series of s and m, total 10 H), 4.07–4.30 (mi 2 H), 4.67–4.69 (m, 1 H), 6.45 (s, 1 H), 6.65 (d, J=1.7 Hz, 1 H), 6.74–6.76 (m, 1 H), 6.84 (d, J=8.8 Hz, 2 H), 7.14 (m, 2 H), 7.24 (m, 2 H), 7.52–7.54 (m, 1 H), 7.94 (d, J=8.8 Hz, 2 H), 8.09 (d, J=8.1 Hz, 1H).

후처리

  1. washwashed with brine (2×100 ml)
  2. dry with materialdried over MgSO4
  3. customThe residue was chromatographed on silica gel with CHCl3-MeOH (20:1) as eluent

출처 및 근거

ORD 기록
ord-ed05b4cc4090449588451e8366e4ee9a
출처 데이터셋
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07179819B2

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