Diisopropylethylamine → HCID 86757204、化合物

HRID 1386919ノート

反応式

HRID 1386919 の反応式
[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]

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 69624973HCID 69624973、化合物HCID 86757205HCID 86757205、化合物

生成物 1

HCID 86757204HCID 86757204、化合物収率 94.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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.

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-7092aa122afd429a911444f23577eb3d
出典データセット
uspto-grants-2001_07
特許番号
US06265572B1

反応ノート

読み込み中…