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1-Hydroxybenzotriazole → 3-{7-[2-(3-aminopyrrolidin-1-yl)-2-oxoethoxy]-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl}-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one

HRID 601362
ノート
印刷プレビュー

反応式

HRID 601362 の反応式
[CH:1]1([CH2:4][NH:5][N:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([OH:16])=[C:8]([C:17]3[NH:22][C:21]4[CH:23]=[CH:24][C:25]([O:27][CH2:28][C:29]([OH:31])=O)=[CH:26][C:20]=4[S:19](=[O:33])(=[O:32])[N:18]=3)[C:7]2=[O:34])[CH2:3][CH2:2]1.Cl.C[N:37]([CH3:46])[CH2:38][CH2:39][CH2:40][N:41]=C=NCC.ON1C2C=CC=CC=2N=N1.C(OC(=O)NC1CCNC1)(C)(C)C>CN(C)C=O.C(OCC)(=O)C>[NH2:41][CH:40]1[CH2:39][CH2:38][N:37]([C:29](=[O:31])[CH2:28][O:27][C:25]2[CH:24]=[CH:23][C:21]3[NH:22][C:17]([C:8]4[C:7](=[O:34])[N:6]([NH:5][CH2:4][CH:1]5[CH2:2][CH2:3]5)[C:15]5[C:10]([C:9]=4[OH:16])=[CH:11][CH:12]=[CH:13][CH:14]=5)=[N:18][S:19](=[O:32])(=[O:33])[C:20]=3[CH:26]=2)[CH2:46]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 136358499[(3-{1-[(cyclopropylmethyl)amino]-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl}-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl)oxy]acetic acid

生成物 1

HCID 136347179
3-{7-[2-(3-aminopyrrolidin-1-yl)-2-oxoethoxy]-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl}-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one
収率 54.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

The product of Example 384B (24 mg, 0,05 mmole), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (16 mg, 0.08 mmol) and 1-hydroxybenzotriazole (14 mg, 0.1 mmol) in N,N-dimethylformamide (2 mL) was added pyrrolidin-3-yl-carbamic acid tert-butyl ester(19 mg, 0.1 mmol). The mixture was stirred for 1 day. The solution was poured into ethyl acetate (40 mL) and washed with saturated aqueous sodium bicarbonate, water, and brine, dried with magnesium sulfate, filtered and concentrated. The residue was triturated with methanol/water and filtered. The solid was treated with hydrochloric acid (1 M in dioxane, 2 mL) and stirred overnight, filtered and washed with ethyl acetate/hexane (1:1) to give title compound (15 mg, 51%). 1H NMR (500 MHz, BENZENE-d6) δ 0.16 (m, 2 H) 0.43 (m, 2 H) 1.01 (m, 1 H) 2.14 (m, 2 H) 2.29 (m, 1 H) 2.89 (d, J=6.84 Hz, 2 H) 3.36 (m, 2 H) 3.81 (m, 2 H) 4.88 (m, 2 H) 7.42 (m, 3 H) 7.61 (m, 1 H) 7.88 (m, 1 H) 8.09 (d, J=8.30 Hz, 1 H) 8.17 (d, J=8.30 Hz, 1 H) 8.28 (s, 3 H) 13.99 (s, 1 H). MS (ESI−) m/z 551 (M−H)−.

後処理

  1. washwashed with saturated aqueous sodium bicarbonate, water, and brine
  2. dry with materialdried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was triturated with methanol/water
  6. filtrationfiltered
  7. additionThe solid was treated with hydrochloric acid (1 M in dioxane, 2 mL)
  8. stirringstirred overnight
  9. filtrationfiltered
  10. washwashed with ethyl acetate/hexane (1:1)

出典と根拠

ORDレコード
ord-19474a84aa6b47a69ee4ede996f024b9
出典データセット
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07902203B2

反応ノート

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