1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1,2,3,4-Tetrahydro-isoquinoline-3-carboxylic acid 4-{[(4-tert-butyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-3-hydroxymethyl-benzylamide

HRID 1592697ノート

反応式

HRID 1592697 の反応式
[NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:11][N:12]([CH2:23][C:24]2[CH:29]=[C:28]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH:27]=[CH:26][N:25]=2)[CH:13]2[C:22]3[N:21]=[CH:20][CH:19]=[CH:18][C:17]=3[CH2:16][CH2:15][CH2:14]2)=[C:7]([CH2:9][OH:10])[CH:8]=1.Cl.[CH2:35]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][CH:37]([C:45](O)=[O:46])[NH:36]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:30]([C:28]1[CH:27]=[CH:26][N:25]=[C:24]([CH2:23][N:12]([CH2:11][C:6]2[CH:5]=[CH:4][C:3]([CH2:2][NH:1][C:45]([CH:37]3[CH2:38][C:39]4[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=4)[CH2:35][NH:36]3)=[O:46])=[CH:8][C:7]=2[CH2:9][OH:10])[CH:13]2[C:22]3[N:21]=[CH:20][CH:19]=[CH:18][C:17]=3[CH2:16][CH2:15][CH2:14]2)[CH:29]=1)([CH3:33])([CH3:32])[CH3:31]

参加物

7

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27241351,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid hydrochlorideHCID 67271580(5-Aminomethyl-2-{[(4-tert-butyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-phenyl)-methanol

生成物 1

HCID 672718111,2,3,4-Tetrahydro-isoquinoline-3-carboxylic acid 4-{[(4-tert-butyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-3-hydroxymethyl-benzylamide収率 28%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

(5-Aminomethyl-2-{[(4-tert-butyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-phenyl)-methanol (0.047 g, 0.11 mmol), (±)-1,2,3,4-tetrahydro-3-isoquinoline carboxylic acid hydrochloride (0.027 g, 0.13 mmol), HOBT (0.017 g, 0.13 mmol), EDCI (0.024 g, 0.13 mmol) and DIPEA (40 μL, 0.26 mmol) in CH2Cl2 (8 mL) were reacted according to General Procedure G. Purification by column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 94:5:1, v/v/v) afforded 1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid 4-{[(4-tert-butyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-3-hydroxymethyl-benzylamide as a white solid (0.018 g, 28%). 1H NMR (CDCl3) δ 1.40 (s, 9H), 1.59 (m, 1H), 1.89-2.02 (m, 2H), 2.22 (m, 1H), 2.69 (m, 1H), 2.79 (m, 1H), 3.22 (dt, 1H, J=12.0, 3.0 Hz), 3.55-3.66 (m, 4H), 3.87 (m, 1H), 3.94 (d, 2H, J=4.5 Hz), 4.06 (d, 2H, J=12.0 Hz), 4.40 (m, 3H), 7.04-7.24 (m, 9H), 7.36 (d, 1H, J=7.5 Hz), 7.52 (br t, 1H), 7.89 (s, 1H), 8.36 (d, 1H, J=6.0 Hz), 8.51 (d, 1H, J=3.0 Hz). HPLC: 89%. ES-MS m/z 604 [M+H]+.

後処理

  1. customPurification by column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 94:5:1, v/v/v)

出典と根拠

ORDレコード
ord-5ec8cc0a4b3a499190a7e0f2fb5bfc3c
出典データセット
uspto-grants-2007_11
特許番号
US07291631B2

反応ノート

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