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1-Hydroxybenzotriazole → HCID 71287916, 화합물

HRID 246145
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HRID 246145 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([OH:23])=O)=[CH:19][N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.Cl.[NH2:33][C@H:34]1[CH2:39][CH2:38][CH2:37][C@H:36]([C:40]([NH2:42])=[O:41])[CH2:35]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:40]([C@H:36]1[CH2:37][CH2:38][CH2:39][C@H:34]([NH:33][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=5)[N:8]([CH3:11])[N:7]=4)[N:13]=3)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:31])[CH3:29])[CH:19]=2)=[O:23])[CH2:35]1)(=[O:41])[NH2:42]
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참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67277232HCID 67277232, 화합물HCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

생성물 1

HCID 71287916
HCID 71287916, 화합물
수율 62%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A 25 mL round-bottomed flask was charged with 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.15 g, 0.33 mmol), trans-3-aminocyclohexanecarboxamide hydrochloride (88 mg, 0.49 mmol), HBTU (155 mg, 0.41 mmol), and HOBT (49 mg, 0.41 mmol). Then added DMF (1.0 mL) followed by N,N-diisopropylethylamine (0.17 mL, 0.97 mmol). The yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (30 mL). The organic layer was washed once with saturated NaHCO3 and water. The combined aqueous layers were back extracted with EtOAc (25 mL). The combined organic layers was dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over SiO2 with EtOAc/hexanes (gradient: 0-100% EtOAc) to afford 119 mg (62%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-3-carbamoyl-cyclohexyl)-amide as a white solid. MS: [M+Na]+=604.

후처리

  1. customthen quenched with water
  2. extractionextracted with EtOAc (30 mL)
  3. washThe organic layer was washed once with saturated NaHCO3 and water
  4. extractionThe combined aqueous layers were back extracted with EtOAc (25 mL)
  5. dry with materialThe combined organic layers was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography over SiO2 with EtOAc/hexanes (gradient: 0-100% EtOAc)

출처 및 근거

ORD 기록
ord-18288707034646c497a819738784ccee
출처 데이터셋
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08658646B2

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