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

HRID 1183894

반응식

HRID 1183894 반응식
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.[Cl:40][C:41]1[CH:49]=[CH:48][CH:47]=[C:46]2[C:42]=1[CH2:43][CH2:44][NH:45]2.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:45]2[C:46]3[C:42](=[C:41]([Cl:40])[CH:49]=[CH:48][CH:47]=3)[CH2:43][CH2:44]2)=[O:10])=[CH:13][C:14]=1[C:29]1[N:33]([CH3:34])[N:32]=[CH:31][CH:30]=1

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6228DimethylformamideHCID 30163064-ChloroindolineHCID 86633178tert-butyl {2-[4-({[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}amino)-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]ethyl}carbamate

생성물 1

HCID 578147084-Chloro-2,3-dihydro-indole-1-carboxylic Acid [4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amide수율 43.5%

시약·촉매·용매 1

HCID 313Hydrochloric Acid촉매

실험 절차

A 1 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 (78.8 μmol) was added to 4-chloroindoline (14.52 mg, 1.2 eq) and stirred at room temperature for 18 hr. To this was added 2.0M hydrochloric acid in ether (197 μL, 5 eq) and the reaction was stirred at room temperature for 24 hr (2-3 drops of concentrated hydrochloric acid was added if the deprotection was incomplete and the resulting mixture was stirred for another 24 hr). The ether and hydrochloric acid were evaporated under a stream of nitrogen and the resulting material was purified by HPLC. The proper fractions were collected and lyophilized to afford the title compound as a white solid in 43.5% yield. LCMS m/z (%)=412 (M+H 35Cl, 100), 414 (M+H 37Cl, 36). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.10-3.24 (m, 4 H), 3.71 (s, 3 H), 4.13-4.21 (m, 4 H), 6.34 (d, J=2.02 Hz, 1 H), 6.96 (d, J=8.08 Hz, 1 H), 7.13-7.21 (m, 2 H), 7.48-7.50 (m, 2 H), 7.64 (dd, J=8.84, 2.78 Hz, 1 H), 7.81 (d, J=7.58 Hz, 1 H), 7.92 (s, 2 H), 8.63 (s, 1 H).

후처리

  1. additionwas added if the deprotection
  2. stirringthe resulting mixture was stirred for another 24 hr)
  3. customThe ether and hydrochloric acid were evaporated under a stream of nitrogen
  4. customthe resulting material was purified by HPLC
  5. customThe proper fractions were collected

출처 및 근거

ORD 기록
ord-810f049871b442eba35e79b2efaee956
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08664258B2

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