Diisopropylethylamine → HCID 86757206、化合物

HRID 1386920ノート

反応式

HRID 1386920 の反応式
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]

参加物

7

反応物 4

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

生成物 1

HCID 86757206HCID 86757206、化合物収率 115.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-24525d5152e447a2bae0a589c55b49c4
出典データセット
uspto-grants-2001_07
特許番号
US06265572B1

反応ノート

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