Diisopropylethylamine → 4-{3-[7-(3-tert-butoxycarbonylamino-cyclopentylcarbamoyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-6-fluoro-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 246315노트

반응식

HRID 246315 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([F:23])[CH:21]=3)[C:16]([C:24]3[N:25]=[C:26]4[C:32]([C:33]([OH:35])=O)=[CH:31][N:30]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:27]4=[N:28][CH:29]=3)=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[C:45]([O:49][C:50](=[O:58])[NH:51][CH:52]1[CH2:56][CH2:55][CH:54]([NH2:57])[CH2:53]1)([CH3:48])([CH3:47])[CH3:46].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([F:23])[CH:21]=3)[C:16]([C:24]3[N:25]=[C:26]4[C:32]([C:33](=[O:35])[NH:57][CH:54]5[CH2:55][CH2:56][CH:52]([NH:51][C:50]([O:49][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:58])[CH2:53]5)=[CH:31][N:30]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:41])([CH3:42])[CH3:43])[C:27]4=[N:28][CH:29]=3)=[N:15]2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45156792tert-Butyl (3-aminocyclopentyl)carbamate--hydrogen chloride (1/1)HCID 712802552-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

생성물 1

HCID 712805284-{3-[7-(3-tert-butoxycarbonylamino-cyclopentylcarbamoyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-6-fluoro-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester수율 109%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A 10 ml round-bottomed flask was charged with 2-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (85 mg, 0.14 mmol) and (3-aminocyclopentyl)-carbamic acid tert-butyl ester hydrochloride (50 mg, 0.21 mmol). Then, DMF (1 ml) was added followed by N,N-diisopropylethylamine (0.07 ml, 0.40 mmol) and HATU (59 mg, 0.155 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over 12 g silica gel with EtOAc/hexanes (gradient: 0-50% EtOAc) to afford 121 mg (99%) of 4-{3-[7-(3-tert-butoxycarbonylamino-cyclopentylcarbamoyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-6-fluoro-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester as a light yellow oil. The isolated product was determined to be a single diastereomer of unknown relative stereochemistry by NMR analysis.

후처리

  1. customthen quenched with water
  2. extractionextracted with diethyl ether (2×)
  3. washThe combined organic layers were washed twice with water and once with brine
  4. dry with materialthen dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed over 12 g silica gel with EtOAc/hexanes (gradient: 0-50% EtOAc)

출처 및 근거

ORD 기록
ord-f13b7efa05d846d5a0336cae31deeac4
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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