3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)benzoyl chloride → 3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-(cyclopropyl)methyl-N-phenylbenzamide

HRID 741639Notes

Reaction equation

[CH:1]1([CH2:4][NH:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.[CH2:12]([N:15]1[C@H:20]([CH3:21])[CH2:19][N:18]([C@H:22]([C:37]2[CH:38]=[C:39]([CH:43]=[CH:44][CH:45]=2)[C:40](Cl)=[O:41])[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([O:29][Si](C(C)(C)C)(C)C)[CH:24]=2)[C@@H:17]([CH3:46])[CH2:16]1)[CH:13]=[CH2:14]>>[CH2:12]([N:15]1[C@H:20]([CH3:21])[CH2:19][N:18]([C@H:22]([C:37]2[CH:38]=[C:39]([CH:43]=[CH:44][CH:45]=2)[C:40]([N:5]([CH2:4][CH:1]2[CH2:2][CH2:3]2)[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:41])[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([OH:29])[CH:24]=2)[C@@H:17]([CH3:46])[CH2:16]1)[CH:13]=[CH2:14]

Participants

Reactant 2

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

HCID 15194687N-(Cyclopropylmethyl)aniline

Product 1

HCID 571507413-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-(cyclopropyl)methyl-N-phenylbenzamide

Procedure

N-(Cyclopropyl)methylaniline 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-(cyclopropyl)methyl-N-phenylbenzamide as an off-white powder. NMR (200 MHz, DMSO-d6): δ0.09 (m, 2H); 0.39 (m, 2H); 0.92 (d, J=6.3 Hz,3H); 0.96 (d, J=6.2 Hz, 3H); 1.28 (m, 1H); 1.69 (dd, J1 =7.4 Hz, J2 =11.5 Hz, 1H); 2.04 (dd, J1 =6.6 Hz, J2 =11.0 Hz, 1H); 2.30 (br d, J=12.1 Hz, 1H); 2.40-2.54 (m, 2H); 2.67 (br d, J=9.8 Hz, 1H); 2.85 (dd, J1 =7.4 Hz, J2 =13.7 Hz, 1H); 3.16 (dd, J1 =4.5 Hz, J2 =14.7 Hz, 1H); 3.72 (d, J=7.0 Hz, 2H); 4.77 (s, 1H); 5.12 (d, J=10.0 Hz, 1H); 5.18 (d, J=15.6 Hz, 1H); 5.70-5.85 (m, 1H); 6.44 (d, J=7.3 Hz, 1H); 6.57 (s, 1H); 6.65 (d, J=8.0 Hz, 1H); 7.02-7.33 (m, 10H); 9.33 (s, 1H). Mass spectrum (CI--CH4) m/e: 510 (M+1, 61%), 356 (42%), 153 (100%). [α]D20 =+8.9° (abs. ethanol, c=1.1). The free amine was dissolved in ethanol and titrated with ethanolic hydrogen chloride to pH 3.75 followed by precipitation with diethyl ether from dichloromethane to give the monohydrochloride salt as a hygroscopic off-white powder. Calc. for C33H39N3O2HCl 1.25 H2O: C, 69.70; H, 7.53; N, 7.39; Cl, 6.23. Found: C, 69.82; H, 7.52; N, 7.36; Cl, 6.28.

Workup

custompurified by the methods

Sources & evidence

ORD record: ord-61ff917ddc8b448392a87be12d804aae
Source dataset: uspto-grants-1996_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05552404

Reaction notes

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