Hydrochloric Acid → 1-(2-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide

HRID 528943노트

반응식

HRID 528943 반응식
[N:1]([CH2:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][N:6]1[C:15]([C:17]1[CH:22]=[C:21]([C:23](=[O:47])[NH:24][S:25]([C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[C:31]([O:38][CH2:39][CH2:40][N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[CH:32]=[CH:33][CH:34]=3)[CH:29]=2)(=[O:27])=[O:26])[CH:20]=[CH:19][C:18]=1[N:48]1[C:52]([CH3:53])=[C:51]([Cl:54])[C:50]([C:55]([N:57]([CH2:62][CH2:63][CH2:64][CH3:65])[CH2:58][CH2:59][CH2:60][CH3:61])=[O:56])=[N:49]1)=[O:16])=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH-].[Na+].Cl>C1COCC1.O>[NH2:1][CH2:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][N:6]1[C:15]([C:17]1[CH:22]=[C:21]([C:23](=[O:47])[NH:24][S:25]([C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[C:31]([O:38][CH2:39][CH2:40][N:41]4[CH2:42][CH2:43][O:44][CH2:45][CH2:46]4)[CH:32]=[CH:33][CH:34]=3)[CH:29]=2)(=[O:27])=[O:26])[CH:20]=[CH:19][C:18]=1[N:48]1[C:52]([CH3:53])=[C:51]([Cl:54])[C:50]([C:55]([N:57]([CH2:62][CH2:63][CH2:64][CH3:65])[CH2:58][CH2:59][CH2:60][CH3:61])=[O:56])=[N:49]1)=[O:16]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 86718907(S)-1-(2-(3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide

생성물 1

HCID 867189081-(2-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide수율 75%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
50 °C

실험 절차

To a solution of (S)-1-(2-(3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (45 mg, 0.049 mmol) and PPh3 (38 mg, 0.15 mmol) in THF (4.0 mL) and water (0.4 mL) was added 1N aq. NaOH solution (0.2 mL, 0.20 mmol). The resulting reaction mixture was heated at 50° C. for 3 h and then acidified (pH=1) with 1N aq. HCl solution. The solvent was removed in vacuo, and the residue was purified by preparative HPLC to give the title compound (33 mg, 72%) as a white solid. 1H NMR (CD3OD, mixture of amide rotamers) δ 9.16 (s, 1H), 8.29-7.88 (m, 4H), 7.83-7.58 (m, 3H), 7.40-7.08 (m, 4H), 6.99 (br s, 1H), 5.04 (br s, 0.5H), 4.76-4.41 (m, 4H), 4.27-2.66 (m, 18.5H), 2.42-2.20 (m, 3H), 1.64-0.72 (m, 13H), 0.60 (br s, 1H); MS(ESI+) m/z 898.1 (M+H)+.

후처리

  1. customThe resulting reaction mixture
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-3069e063c18d4a4a9576286fa8da8894
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346795B2

반응 노트

불러오는 중…