N,N-Dimethyl-1,3-propanediamine → (RS)-2-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluorophenyl)-N-(3-dimethylamino-propyl)acetamide

HRID 18068

반응식

HRID 18068 반응식
[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][NH2:6].Cl.CN(C)CCCN=C=NCC.O.OC1C2N=NNC=2C=CC=1.Cl.[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([CH:39]([C:56]2[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][CH:57]=2)[N:40]2[CH2:43][CH:42]([CH:44]([C:48]3[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=3)[C:45](O)=[O:46])[CH2:41]2)=[CH:35][CH:34]=1>ClCCl.C(N(CC)CC)C>[Cl:62][C:59]1[CH:60]=[CH:61][C:56]([CH:39]([C:36]2[CH:35]=[CH:34][C:33]([Cl:32])=[CH:38][CH:37]=2)[N:40]2[CH2:43][CH:42]([CH:44]([C:48]3[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=3)[C:45]([NH:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:7])[CH3:1])=[O:46])[CH2:41]2)=[CH:57][CH:58]=1

참가 물질

7

반응물 4

HCID 7993N,N-Dimethyl-1,3-propanediamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68584946{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-(3,5-difluorophenyl)acetic acid hydrochlorideHCID 178526939HCID 178526939, 화합물

생성물 1

HCID 22506766(RS)-2-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluorophenyl)-N-(3-dimethylamino-propyl)acetamide

시약·촉매·용매 2

HCID 6344Dichloromethane용매2회HCID 8471Triethylamine용매

반응 조건

온도
20 °C

실험 절차

(RS)-2-{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-2-(3,5-difluorophenyl)-N-(3-dimethyl-aminopropyl)acetamide may be prepared in the following manner: 0.015 cm3 of N,N-dimethylpropane-1,3-diamine, 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 (of 12 mm in diameter) filled with 4 cm3 of silica (0.060-0.200 mm) conditioned with dichloromethane with the aid of a vacuum apparatus, eluting with dichloromethane between 0 and 6 cm3 and then with a dichloromethane-methanol (95-5 by volume) mixture. The fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. 33 mg [lacuna] (RS)-2-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluorophenyl)-N-(3-dimethylamino-propyl)acetamide are thus obtained in the form of white crystals [1H NMR spectrum (300 MHz, CDCl3, with addition of a few drops of CD3COOD d4, δ in ppm): 1.91 (mt: 2H); 2.71 (s: 6H); 2.95 (mt: 2H); from 3.15 to 3.40 (mt 2H); from 3.40 to 3.60 (mt: 1H); from 3.60 to 3.80 (mt: 2H); 4.00 (mt: 2H); 4.28 (d, J=10.5 Hz: 1H); 5.22 (s 1H); 6.68 (tt, J=9 and 2.5 Hz: 1H); 6.90 (mt: 2H); 7.33 (mt: 4H); 7.46 (d, J=8 Hz: 4H)].

후처리

  1. customThe solution obtained
  2. additionfilled with 4 cm3 of silica (0.060-0.200 mm)
  3. washeluting with dichloromethane between 0 and 6 cm3
  4. additionThe fractions containing only the desired product
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C

출처 및 근거

ORD 기록
ord-2015299e6b254d1bb829107a2b7a7309
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741316B2

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