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Methylamine → (RS)-2-{1-(bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluorophenyl)-N-methylacetamide

HRID 985473
ノート
印刷プレビュー

反応式

HRID 985473 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[N:9]2[CH2:12][CH:11]([CH:13]([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=3)[C:14]([NH:16][CH2:17]CC)=[O:15])[CH2:10]2)=[CH:4][CH:3]=1.CN.Cl.CN(C)CCCN=C=NCC.O.OC1C2N=NNC=2C=CC=1.Cl.ClC1C=CC(C(C2C=CC(Cl)=CC=2)N2CC(C(C3C=C(F)C=C(F)C=3)C(O)=O)C2)=CC=1>O1CCCC1.ClCCl.C(N(CC)CC)C>[Cl:34][C:31]1[CH:30]=[CH:29][C:28]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[N:9]2[CH2:10][CH:11]([CH:13]([C:20]3[CH:21]=[C:22]([F:27])[CH:23]=[C:24]([F:26])[CH:25]=3)[C:14]([NH:16][CH3:17])=[O:15])[CH2:12]2)=[CH:33][CH:32]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 6329MethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22506657(RS)-2-{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-2-(3,5-difluorophenyl)-N-propylacetamideHCID 68584946{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-(3,5-difluorophenyl)acetic acid hydrochlorideHCID 178526939HCID 178526939、化合物

生成物 1

HCID 22506786
(RS)-2-{1-(bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluorophenyl)-N-methylacetamide

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒

反応条件

温度
20 °C

実験手順

(RS)-2-{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-2-(3,5-difluorophenyl)-N-propylacetamide may be prepared in the following manner: 0.050 cm3 of a 2 M solution of methylamine in tetrahydrofuran, 29 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 0.028 cm3 of triethylamine and 1.5 mg of hydroxybenzotriazole hydrate are successively added to a solution of 50 mg of (RS)-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-(3,5-difluorophenyl)acetic acid hydrochloride in 2 cm3 of anhydrous dichloromethane, at a temperature in the region of 20° C. The solution obtained is stirred at a temperature in the region of 20° C. for about 12 hours. The reaction medium is deposited on a Varian cartridge (6 cm3) filled with 3 g of fine silica (0.040-0.063 mm) conditioned and eluted with dichloromethane with the aid of a Duramat pump. The fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. 19 mg of (RS)-2-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluorophenyl)-N-methylacetamide are thus obtained in the form of a white solid [1H NMR spectrum (300 MHz, CDCl3, δ in ppm): 2.66 (mt: 1H); 2.76 (d, J=5 Hz: 3H); 2.93 (mt: 1H); 3.10 (mt: 2H); 3.44 (broad t, J=7.5 Hz: 1H); 3.59 (d, J=10.5 Hz: 1H); 4.28 (s: 1H); 5.41 (unresolved complex: 1H); 6.71 (tt, J=9 and 2.5 Hz: 1H); 6.83 (mt: 2H); from 7.20 to 7.35 (mt: 8H)].

後処理

  1. customThe solution obtained
  2. additionfilled with 3 g of fine silica (0.040-0.063 mm)
  3. washeluted with dichloromethane with the aid of a Duramat pump
  4. additionThe fractions containing only the desired product
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C

出典と根拠

ORDレコード
ord-da686cda8c0f44b38df889a9c362ca84
出典データセット
uspto-grants-2005_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06872717B2

反応ノート

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