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

HRID 354438ノート

反応式

HRID 354438 の反応式
[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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-8b4e88936d1041b5bccada2df3fb6a89
出典データセット
uspto-grants-2004_06
特許番号
US06756378B2

反応ノート

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