Diisopropylethylamine → HCID 86757204, 화합물

HRID 1386919노트

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HRID 1386919 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

HCID 86757204HCID 86757204, 화합물수율 94.6%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-7092aa122afd429a911444f23577eb3d
출처 데이터셋
uspto-grants-2001_07
특허 번호
US06265572B1

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