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

HRID 354438노트

반응식

HRID 354438 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.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH:27][C:28](=[O:42])[NH:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][C:37](O)=[O:38])=[CH:32][C:31]=1[O:40][CH3:41].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C1C=CN=CC=1)C.CCOC(C)=O.CN(C=O)C>[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH:27][C:28](=[O:42])[NH:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][C:37]([N:5]2[CH2:6][C:2]([F:1])([F:19])[CH2:3][CH:4]2[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)=[O:38])=[CH:32][C:31]=1[O:40][CH3:41]

참가 물질

8

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 235118674-[N'-(2-chlorophenyl)ureido]-3-methoxyphenylacetic acidHCID 23512388Methyl 4-(4,4-difluoro-2-pyrrolidinylmethoxy)benzoate

생성물 1

HCID 69333413methyl 4-[1-[4-[N'-(2-chlorophenyl)ureido]-3-methoxy phenylacetyl]-4,4-difluoro-2-pyrrolidinylmethoxy]benzoate수율 97%

시약·촉매·용매 3

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

실험 절차

A mixture of methyl 4-(4,4-difluoro-2-pyrrolidinylmethoxy)benzoate (229 mg, 0.845 mmol), 4-[N′-(2-chlorophenyl)ureido]-3-methoxyphenylacetic acid (283 mg, 0.845 mmol), EDC.HCl (243 mg, 1.27 mmol), HOBt (cat.), DMAP (cat.), and DMF (10 ml) was stirred overnight. The mixture was diluted with EtOAc (300 ml). The solution was washed with brine (2×100 ml), dried over MgSO4, and concntrated in vacuo. The residue was chromatographed on silica gel with CHCl3-EtOAc (20:1 to 4:1) as eluent to give methyl 4-[1-[4-[N′-(2-chlorophenyl)ureido]-3-methoxyphenylacetyl]-4,4-difluoro-2-pyrrolidinylmethoxy]benzoate (482 mg, 97%) as a colorless viscous solid. 1H-NMR (CDCl3) δ2.50-2.67 (m, 2 H), 3.54-4.71 (series of m, 13 H), 6.69 (d, J=1.5 Hz, 1 H), 6.76 (d, J=8.3 Hz, 1 H), 6.84 (d, J=8.8 Hz, 2 H), 6.98 (dt, J=7.8, 1.5 Hz, 1 H), 7.23-7.27 (m, 1 H), 7.33 (d, J=8.3 Hz, 1 H), 7.39 (m, 2 H), 7.94 (d, J=8.8 Hz, 2 H), 8.00 (d, J=8.3 Hz, 1 H), 8.19 (dd, J=8.3, 1.5 Hz, 1 H).

후처리

  1. washThe solution was washed with brine (2×100 ml)
  2. dry with materialdried over MgSO4
  3. customThe residue was chromatographed on silica gel with CHCl3-EtOAc (20:1 to 4:1) as eluent

출처 및 근거

ORD 기록
ord-8b4e88936d1041b5bccada2df3fb6a89
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06756378B2

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