Hydrochloric Acid → (2S)-N-[(2S)-1-{[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl] (methyl)amino}-3-methyl-1-oxobutan-2-yl]-2-methylpiperidine-2-carboxamide, hydrochloride salt

HRID 74804Notes

Reaction equation

HRID 74804 reaction equation
[CH:1]1([CH2:8][CH2:9][NH:10][C:11](=[O:58])[C@H:12]([CH3:57])[C@H:13]([C@@H:16]2[CH2:20][CH2:19][CH2:18][N:17]2[C:21](=[O:56])[CH2:22][C@@H:23]([O:54][CH3:55])[C@@H:24]([N:29]([CH3:53])[C:30](=[O:52])[C@@H:31]([NH:35][C:36]([C@:38]2([CH3:51])[CH2:43][CH2:42][CH2:41][CH2:40][N:39]2C(OC(C)(C)C)=O)=[O:37])[CH:32]([CH3:34])[CH3:33])[C@@H:25]([CH3:28])[CH2:26][CH3:27])[O:14][CH3:15])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=[CH:2]1.[ClH:59]>O1CCOCC1>[ClH:59].[CH:1]1([CH2:8][CH2:9][NH:10][C:11](=[O:58])[C@H:12]([CH3:57])[C@H:13]([C@@H:16]2[CH2:20][CH2:19][CH2:18][N:17]2[C:21](=[O:56])[CH2:22][C@@H:23]([O:54][CH3:55])[C@@H:24]([N:29]([CH3:53])[C:30](=[O:52])[C@@H:31]([NH:35][C:36]([C@:38]2([CH3:51])[CH2:43][CH2:42][CH2:41][CH2:40][NH:39]2)=[O:37])[CH:32]([CH3:34])[CH3:33])[C@@H:25]([CH3:28])[CH2:26][CH3:27])[O:14][CH3:15])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=[CH:7]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86685759tert-butyl (2S)-2-{[(2S)-1-{[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(cyc lohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl](methyl)amino}-3-methyl-1-oxobutan-2-yl]carbamoyl]-2-methylpiperidine-1-carboxylate

Product 1

HCID 131731854(2S)-N-[(2S)-1-{[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl] (methyl)amino}-3-methyl-1-oxobutan-2-yl]-2-methylpiperidine-2-carboxamide, hydrochloride saltYield 89%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

According to the general procedure C, from #177 (143 mg, 0.176 mmol, 1 eq.) and 4M solution of hydrochloric acid in dioxane (2.0 mL) was synthesized the desired material as a gum (145 mg). A portion of this crude residue (25 mg) was azeotroped with a mixture of methanol/acetonitrile to afford #178 (20 mg, 89% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6), δ 8.96-9.07 (m), 8.79-8.96 (m), 8.58 (d), 8.02-8.08 (m), 7.77-7.83 (m), 7.25-7.31 (m), 7.19-7.24 (m), 6.56-6.67 (m), 6.12-6.21 (m), 5.13-5.22 (m), 4.72-4.81 (m), 4.63-4.70 (m), 4.50-4.59 (m), 4.07-4.16 (m), 3.98-4.05 (m), 3.80-3.86 (m), 3.55-3.76 (m), 3.46-3.54 (m), 3.38-3.44 (m), 3.26-3.35 (m), 3.18-3.24 (m), 3.05-3.18 (m), 2.98-3.04 (m), 2.40-2.55 (m), 2.27-2.35 (m), 2.08-2.27 (m), 1.74-1.98 (m), 1.50-1.74 (m), 1.20-1.46 (m), 0.73-1.16 (m). LC-MS (Protocol Q1): m/z 714.6 [M+H+], retention time=0.76 minutes. HPLC (Protocol U): m/z 714.5 [M+H+] retention time=7.124 minutes (purity=91%).

Workup

  1. customA portion of this crude residue (25 mg) was azeotroped with a mixture of methanol/acetonitrile

Sources & evidence

ORD record
ord-97fe4c34a88f4be89c1b31d45096ef9e
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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