Diisopropylethylamine → HCID 86757206, compound

HRID 1386920Notes

Reaction equation

HRID 1386920 reaction equation
CC(C)(OC([N:7]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[C@H:8]1[C:19]([OH:21])=O)=O)C.Cl.[CH3:24][C:25]([O:28][C:29]([C@@H:31]1[CH2:47][S:46][S:45][CH2:44][C@H:43]([NH2:48])[C:42](=[O:49])[NH:41][CH2:40][CH2:39][C:34]2([CH2:38][CH2:37][CH2:36][CH2:35]2)[C:33](=[O:50])[NH:32]1)=[O:30])([CH3:27])[CH3:26].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH3:27][C:25]([O:28][C:29]([C@@H:31]1[CH2:47][S:46][S:45][CH2:44][C@H:43]([NH:48][C:19]([C@@H:8]2[C@@H:9]([C:12]3[CH:13]=[CH:14][C:15]([OH:18])=[CH:16][CH:17]=3)[CH2:10][CH2:11][NH:7]2)=[O:21])[C:42](=[O:49])[NH:41][CH2:40][CH2:39][C:34]2([CH2:35][CH2:36][CH2:37][CH2:38]2)[C:33](=[O:50])[NH:32]1)=[O:30])([CH3:24])[CH3:26]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9972479HCID 9972479, compoundHCID 86757205HCID 86757205, compound

Product 1

HCID 86757206HCID 86757206, compoundYield 115.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To the mixture of (2S,3R)-1-[(1,1-dimethylethoxy)carbonyl]-3-(4-hydroxyphenyl)pyrolidine-2-carboxylic acid (46 mg, 0.15 mmol) and (8R,13R)-13-amino-6,14-dioxo-10,11-dithia-7,15-diazaspiro[4.12]heptadecane-8-carboxylic acid 1,1-dimethylethyl ester hydrochloride 70 mg, 0.15 mmol), prepared in Example 6, in 0.5 mL of DMF was added DIPEA (58 mg, 0.45 mmol) and HBTU (59 mg, 0.15 mmol). The solution was stirred at room temperature for 3 hours and was diluted with water to 3 mL. The resulting white precipitate was collected and was dried over night at reduced pressure to give 105 mg of (8R,13R)-13-[[[3(R)-(4-hydroxyphenyl)-2(S)-pyrrolidinyl]carbonyl]amino]-6,14-dioxo-10,11-dithia-7,15-diazaspiro[4.12]heptadecane-8-carboxylic acid 1,1-dimethylethyl ester as a white solid. This dried solid (85 mg) was the dissolved in 2 mL of dichloromethane and the solution was treated with 4 N HCl in dioxane (2 mL). The solution was stirred overnight and the solvent was then removed. The residue was purified by reversed-phase HPLC (5-95% of acetonitrile containing 0.75% of TFA in water oevr 40 min linear gradient) to give (8R,13R)-13-[[[3(R)-(4-hydroxyphenyl)-2(S)-pyrrolidinyl]carbonyl]amino]-6,14-dioxo-10,11-dithia-7,15-diazaspiro[4.12]heptadecane-8-carboxylic acid as a white solid (58 mg). HRMS (M+H): Obs. 551.2017, Calcd.551.1998.

Workup

  1. customThe resulting white precipitate was collected
  2. customwas dried over night at reduced pressure

Sources & evidence

ORD record
ord-24525d5152e447a2bae0a589c55b49c4
Source dataset
uspto-grants-2001_07
Patent number
US06265572B1

Reaction notes

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