1-Hydroxybenzotriazole → tert-butyl 5-(1-(4-methoxybenzyl)-4-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

HRID 2241348노트

반응식

HRID 2241348 반응식
[CH3:1][O:2][C:3]1[CH:42]=[CH:41][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10]([N:26]3[CH2:30][CH:29]4[CH2:31][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:33][CH:28]4[CH2:27]3)=[N:9]2)=[CH:5][CH:4]=1.[F:43][C:44]1[CH:49]=[CH:48][C:47]([N:50]2[C:55](=[O:56])[C:54]([C:57](O)=[O:58])=[CH:53][CH:52]=[N:51]2)=[CH:46][CH:45]=1.Cl.C(N=C=NCCCN(C)C)C.N1(O)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C>[F:25][C:19]1[CH:20]=[C:21]([NH:24][C:57]([C:54]2[C:55](=[O:56])[N:50]([C:47]3[CH:48]=[CH:49][C:44]([F:43])=[CH:45][CH:46]=3)[N:51]=[CH:52][CH:53]=2)=[O:58])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:42][CH:41]=3)[N:9]=[C:10]([N:26]3[CH2:30][CH:29]4[CH2:31][N:32]([C:34]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:35])[CH2:33][CH:28]4[CH2:27]3)[C:11]=12

참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 667671712-(4-Fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acidHCID 68514742tert-butyl 5-(4-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

생성물 1

HCID 68512270tert-butyl 5-(1-(4-methoxybenzyl)-4-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate수율 68.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A round-bottomed flask was charged with tert-butyl 5-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (44.8 mg, 0.0780 mmol), 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (54.8 mg, 0.234 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (74.7 mg, 0.390 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (52.7 mg, 0.390 mmol), N-ethyl-N-isopropylpropan-2-amine (101 mg, 0.780 mmol) and DMF (10 mL). The reaction mixture was stirred at ambient temperature overnight. The reaction was partitioned between EtOAc and H2O. The phases were separated and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated. The crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product (42.5 mg, 68.9%). LRMS (APCI pos): m/e 691 (M−99).

후처리

  1. customThe reaction was partitioned between EtOAc and H2O
  2. customThe phases were separated
  3. extractionthe aqueous phase was re-extracted with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1

출처 및 근거

ORD 기록
ord-7388f82a724b45f7bd1adb2696009546
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07723330B2

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