N-Methylbenzeneethanamine → (+)-3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-methyl-N-phenethylbenzamide

HRID 741636Notes

Reaction equation

[CH3:1][NH:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:11]([N:14]1[C@H:19]([CH3:20])[CH2:18][N:17]([C@H:21]([C:36]2[CH:37]=[C:38]([CH:42]=[CH:43][CH:44]=2)[C:39](Cl)=[O:40])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][Si](C(C)(C)C)(C)C)[CH:23]=2)[C@@H:16]([CH3:45])[CH2:15]1)[CH:12]=[CH2:13]>>[CH2:11]([N:14]1[C@H:19]([CH3:20])[CH2:18][N:17]([C@H:21]([C:36]2[CH:37]=[C:38]([CH:42]=[CH:43][CH:44]=2)[C:39]([N:2]([CH3:1])[CH2:3][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:40])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=2)[C@@H:16]([CH3:45])[CH2:15]1)[CH:12]=[CH2:13]

Participants

Reactant 2

HCID 11503N-Methylbenzeneethanamine

HCID 111350383-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)benzoyl chloride

Product 1

HCID 11827173(+)-3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-methyl-N-phenethylbenzamide

Procedure

N-Methylphenethylamine was coupled with 3-((αR)-α-((2S,5R)-4-allyl-2.5-dimethyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)benzoyl chloride, deprotected and purified by the methods described in Example 10 to give (+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-methyl-N-phenethylbenzamide as a light yellow powder. NMR (300 MHz, DMSO-d6, 80° C.): δ0.91 (d, J=5.5 Hz, 3H); 1.08 (d, J=6.3 Hz, 3H); 1.87 (dd, J1 =7.1 Hz, J2 =11.2 Hz, 1H); 2.09 (dd, J1 =7.1 Hz, J2 =11.0 Hz, 1H); 2.58 (d, J=11.3 Hz, 1H); 2.67 (m, 1H); 2.76 (dd, J1 =6.2 Hz, J2 =13.2 Hz, 1H); 2.77-2.87 (m, 4H); 2.89 (s, 3H); 3.18 (dd, J1 =5.5 Hz, J2 =14.2 Hz, 1H); 3.55 (br s, 2H); 4.97 (s, 1H); 5.10 (d, J=10.2 Hz, 1H); 5.16 (d, J=17.3 Hz, 1H); 5.74-5.89 (m, 1H); 6.65-6.13 (m, 3H); 7.07-7.41 (m, 9H); 7.43 (d, J=7.9 Hz, 1H); 9.07 (s,1H). Mass spectrum (CI--CH4) m/e: 498 (M+1, 88%), 344 (22%), 153 (100%. [α]D20 =+3.8° )ethanol, c=1.25). The free amine (0.232 g) was dissolved in ethanol and titrated with ethanolic hydrogen chloride to pH 3.9 followed by precipitation with diethyl ether from dichloromethane to give 0.205 g of the monohydrochloride salt as a hygroscopic light yellow powder. Calc. for C32H39N3O2HCl H2O: C, 69.61; H, 7.67; N, 7.61: Cl, 6.42. Found: C, 69.51: H, 7.73; N, 7.47: Cl, 6.52.

Workup

custompurified by the methods

Sources & evidence

ORD record: ord-b3d4c798efe5464c9e3cee2d047faaac
Source dataset: uspto-grants-1996_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05552404

Reaction notes

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