N-Isopropylaniline → 3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-isopropyl-N-phenylbenzamide

HRID 741641Notes

Reaction equation

[CH:1]([NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[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:4]([CH:1]([CH3:3])[CH3:2])[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 13032N-Isopropylaniline

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

Product 1

HCID 572952293-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-isopropyl-N-phenylbenzamide

Procedure

N-Isopropylaniline was then 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-isopropyl-N-phenylbenzamide as an off-white solid. NMR (200 MHz, DMSO-d6): δ0.92 (d, J=6.1 Hz, 3H); 0.99 (d, J=5.9 Hz, 3H); 1.11 (d, J=6.9 Hz, 6H); 1.70 (dd, J1 =7.2 Hz, J2 =11.1 Hz, 1H); 2.07 (dd, J1 =7.6 Hz, J2 =10.6 Hz, 1H); 2.33 (br d, J=9.9 Hz, 1H); 2.42-2.54 (m, 2H); 2.68 (br d, J=10.4 Hz, 1H); 2.85 (dd, J1 =6.5 Hz, J2 =13.9 Hz, 1H); 3.16 (dd, J1 =4.9 Hz, J2 =14.1 Hz, 1H); 4.75 (s, 1H); 4.85 (m, 1H); 5.10 (d, J=10.2 Hz, 1H); 5.18 (d, J=16.8 Hz, 1H); 5.70-5.84 (m, 1H); 6.50 (d, J=7.1 Hz, 1H); 6.59 (s, 1H); 6.65 (d, J=8.2 Hz, 1H); 7.03-7.32 (m, 10H); 9.33 (s, 1H). Mass spectrum (CI--CH4) m/e: 498 (M+1, 100%), 344 (43%), 153 (76%). [α]D20 =+6.4° (abs. ethanol, c=1.4). The free amine was dissolved in ethanol and titrated with ethanolic hydrogen chloride to pH 4.0 followed by precipitation with diethyl ether from dichloromethane to give the monohydrochloride salt as a hygroscopic off-white powder. Calc. for C32H39N3O2HCl 0.5 H2O: C, 70.76; H, 7.61; N, 7.74; Cl, 6.53. Found: C, 71.01; H, 7.83; N, 7.49; Cl, 6.41.

Workup

custompurified by the methods

Sources & evidence

ORD record: ord-ce25a7b5ea2a4a08ae5488db0867125e
Source dataset: uspto-grants-1996_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05552404

Reaction notes

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