Triethylamine → 4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-1-[3-((3S,4S)-3-hydroxy-4-methyl-piperidin-1-yl)-propyl]-3-methyl-piperazin-2-one

HRID 559365ノート

反応式

HRID 559365 の反応式
Cl.Cl.[OH:3][C@H:4]1[C@@H:9]([CH3:10])[CH2:8][CH2:7][N:6]([CH2:11][CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][NH:17][CH:16]([CH3:20])[C:15]2=[O:21])[CH2:5]1.[Cl:22][C:23]1[CH:24]=[C:25]([CH:31]=[CH:32][C:33]=1[Cl:34])[CH:26]=[CH:27][C:28](O)=[O:29].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O>[Cl:22][C:23]1[CH:24]=[C:25](/[CH:26]=[CH:27]/[C:28]([N:17]2[CH2:18][CH2:19][N:14]([CH2:13][CH2:12][CH2:11][N:6]3[CH2:7][CH2:8][C@H:9]([CH3:10])[C@H:4]([OH:3])[CH2:5]3)[C:15](=[O:21])[CH:16]2[CH3:20])=[O:29])[CH:31]=[CH:32][C:33]=1[Cl:34]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 145483-(3,4-Dichlorophenyl)prop-2-enoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 669992801-[3-((3S,4S)-3-hydroxy-4-methyl-piperidin-1-yl)-propyl]-3-methyl-piperazin-2-one dihydrochloride

生成物 1

HCID 575503864-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-1-[3-((3S,4S)-3-hydroxy-4-methyl-piperidin-1-yl)-propyl]-3-methyl-piperazin-2-one

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a suspension of (3S,4S)-4-methyl-piperidin-3-ol hydrochloride (intermediate 26; 0.04 g, 0.3 mmol) in dichloromethane (1 ml) was added triethylamine (0.04 ml, 0.3 mmol) and acetic acid (0.03 ml, 0.5 mmol) followed by a solution of crude 2-methyl-3-oxo-4-(3-oxo-propyl)piperazine-1-carboxylic acid tert-butyl ester (intermediate 14c; 0.08 g, 0.3 mmol) in dichloromethane (1 ml). Sodium triacetoxyborohydride (0.07 g, 0.4 mmol) was then added and the mixture stirred for 2 h, after which time the mixture was washed with saturated aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated. The crude residue was then treated with HCl in dioxane (2 ml, 4N) and stirred for 30 minutes after which time the reaction was concentrated to afford crude 1-[3-((3S,4S)-3-hydroxy-4-methyl-piperidin-1-yl)-propyl]-3-methyl-piperazin-2-one dihydrochloride as a white powder (0.1 g). To a solution of crude 1-[3-((3S,4S)-3-hydroxy-4-methyl-piperidin-1-yl)-propyl]-3-methyl-piperazin-2-one dihydrochloride (0.03 g, 0.1 mmol) in N,N-dimethylformamide (0.8 ml) was added 3,4-dichlorocinnamic acid (0.02 g, 0.1 mmol), triethylamine (0.05 ml, 0.4 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluoro-phosphate (0.04 g, 0.1 mmol) and the reaction shaken for 1 h, after which time the reaction mixture was directly purified by preparative HPLC. This afforded the titled product as a colorless gum. MS (ISP)=468.1 (M+H)+.

後処理

  1. customafter which time the reaction mixture was directly purified by preparative HPLC

出典と根拠

ORDレコード
ord-622343f001e64a5bbf89337e46c1c4fb
出典データセット
uspto-grants-2011_11
特許番号
US08063042B2

反応ノート

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