Diisopropylethylamine → HCID 86757204, compound

HRID 1386919Notes

Reaction equation

HRID 1386919 reaction equation
[CH3:1][C:2]([CH3:21])([CH3:20])[C:3]([N:5]1[CH2:9][CH2:8][C@H:7]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[C@H:6]1[C:17](O)=[O:18])=[O:4].Cl.[CH3:23][C:24]([O:27][C:28]([C@@H:30]1[CH2:46][S:45][S:44][CH2:43][C@H:42]([NH2:47])[C:41](=[O:48])[NH:40][CH2:39][CH2:38][C:33]2([CH2:37][CH2:36][CH2:35][CH2:34]2)[C:32](=[O:49])[NH:31]1)=[O:29])([CH3:26])[CH3:25].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>[CH3:26][C:24]([O:27][C:28]([C@@H:30]1[CH2:46][S:45][S:44][CH2:43][C@H:42]([NH:47][C:17]([C@@H:6]2[C@@H:7]([C:10]3[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=3)[CH2:8][CH2:9][N:5]2[C:3](=[O:4])[C:2]([CH3:20])([CH3:1])[CH3:21])=[O:18])[C:41](=[O:48])[NH:40][CH2:39][CH2:38][C:33]2([CH2:34][CH2:35][CH2:36][CH2:37]2)[C:32](=[O:49])[NH:31]1)=[O:29])([CH3:23])[CH3:25]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69624973HCID 69624973, compoundHCID 86757205HCID 86757205, compound

Product 1

HCID 86757204HCID 86757204, compoundYield 94.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of (2S,3R)-1-(2,2-dimethyl-1-oxopropyl)-3-(4-hydroxyphenyl)pyrolidine-2-carboxylic acid (45 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 98 mg of (8R,13R)-13-[[[1-(2,2-dimethyl-1-oxopropyl)-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 was the dissolved in 1 mL of dichloromethane and the solution was treated with 4 N HCl in dioxane (2 mL). The solution was stirred overnight and was concentrated. The residue was purified by reversed phase HPLC (5-95% of acetonitrile containing 0.75% of TFA in water over 40 min linear gradient) to give (8R,13R)-13-[[[1-(2,2-dimethyl-1-oxopropyl)-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 white solid (9 mg). HRMS (M+H): Obs. 635.2543, Calcd. 635.2573.

Workup

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

Sources & evidence

ORD record
ord-7092aa122afd429a911444f23577eb3d
Source dataset
uspto-grants-2001_07
Patent number
US06265572B1

Reaction notes

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