Hydrochloric Acid → 3,4-Dihydro-1H-isoquinoline-2-carboxylic Acid [4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amide

HRID 521620

反応式

HRID 521620 の反応式
O=C1CCC(=O)N1O[C:9]([NH:11][C:12]1[CH:28]=[CH:27][C:15]([O:16][CH2:17][CH2:18][NH:19]C(=O)OC(C)(C)C)=[C:14]([C:29]2[N:33]([CH3:34])[N:32]=[CH:31][CH:30]=2)[CH:13]=1)=[O:10].CN(C)C=O.[CH2:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH2:43][CH2:42][NH:41]1.Cl.CCOCC>Cl>[NH2:19][CH2:18][CH2:17][O:16][C:15]1[CH:27]=[CH:28][C:12]([NH:11][C:9]([N:41]2[CH2:42][CH2:43][C:44]3[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=3)[CH2:40]2)=[O:10])=[CH:13][C:14]=1[C:29]1[N:33]([CH3:34])[N:32]=[CH:31][CH:30]=1

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6228DimethylformamideHCID 70461,2,3,4-TetrahydroisoquinolineHCID 86633178tert-butyl {2-[4-({[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}amino)-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]ethyl}carbamate

生成物 1

HCID 578145663,4-Dihydro-1H-isoquinoline-2-carboxylic Acid [4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amide収率 42.9%

試薬・触媒・溶媒 1

HCID 313Hydrochloric Acid触媒

実験手順

A 2 mL aliquot of tert-butyl {2-[4-({[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}amino)-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]ethyl}carbamate in dimethylformamide (60.0 μmol) was added to 1,2,3,4-tetrahydroisoquinoline (9.59 mg, 1.2 eq) and stirred at room temperature for 18 hr. To this was added 2.0M hydrochloric acid in ether (150 μL, 5 eq) and the reaction was stirred at room temperature for 60 hr. Some of the deprotections were incomplete so 2-3 drops of concentrated hydrochloric acid was added to these and they were stirred for another 24 hr. The ether and hydrochloric acid were evaporated under a stream of nitrogen and it was purified by HPLC. The proper fractions were collected and lyophilized to afford the title compound as a white solid in 42.9% yield. LCMS m/z (%)=392 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.85 (t, J=5.81 Hz, 2H), 3.09-3.17 (m, 2H), 3.69 (t, J=5.6 Hz, 2H), 3.69 (s, 3H), 4.12 (t, J=5.56 Hz, 2H), 4.63 (s, 2H), 6.32 (d, J=2.02 Hz, 1H), 7.13 (d, J=9.09 Hz, 1H), 7.19 (s, 3H), 7.43 (d, J=2.53 Hz, 1H), 7.47 (d, J=1.52 Hz, 1H), 7.57 (dd, J=9.09, 3.03 Hz, 1H), 7.87 (s, 2H), 8.60 (s, 1H).

後処理

  1. stirringthe reaction was stirred at room temperature for 60 hr
  2. additionwas added to these and they
  3. stirringwere stirred for another 24 hr
  4. customThe ether and hydrochloric acid were evaporated under a stream of nitrogen and it
  5. customwas purified by HPLC
  6. customThe proper fractions were collected

出典と根拠

ORDレコード
ord-636035a3edc544b798a520fa8112af10
出典データセット
uspto-grants-2016_05
特許番号
US09328107B2

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