Water → 1-(1-Methyl-6-(2-oxa-6-azaspiro[3,3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

HRID 75313노트

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HRID 75313 반응식
[CH3:1][Mg]Br.[CH3:4][N:5]1[C:13]2[C:8](=[N:9][C:10]([C:21]#[N:22])=[C:11]([N:14]3[CH2:20][C:16]4([CH2:19][O:18][CH2:17]4)[CH2:15]3)[CH:12]=2)[CH:7]=[CH:6]1.[BH4-].[Na+].O>C1COCC1>[CH3:4][N:5]1[C:13]2[C:8](=[N:9][C:10]([CH:21]([NH2:22])[CH3:1])=[C:11]([N:14]3[CH2:20][C:16]4([CH2:19][O:18][CH2:17]4)[CH2:15]3)[CH:12]=2)[CH:7]=[CH:6]1

참가 물질

6

반응물 4

HCID 962WaterHCID 4311764Sodium borohydrideHCID 867080111-Methyl-6-(2-oxa-6-azaspiro[3,3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridine-5-carbonitrileHCID 178418573HCID 178418573, 화합물

생성물 1

HCID 867080131-(1-Methyl-6-(2-oxa-6-azaspiro[3,3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine수율 47%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
40 °C

실험 절차

Methylmagnesium bromide (1.56 mL, 2.18 mmol) was added slowly to a stirred solution of 1-methyl-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile (222 mg, 0.873 mmol) in THF (20 mL). The reaction was stirred at 40° C. for 1.5 hours, then cooled to 0° C. and quenched with MeOH (10 mL). After 10 minutes, sodium tetrahydroborate (83 mg, 2.18 mmol) was added. The reaction mixture was stirred for 20 minutes. Water (1 mL) was added and the reaction mixture was stirred for an additional 10 minutes. The reaction mixture was dried over MgSO4, filtered through Celite, and concentrated. The crude product was purified by basic silica column chromatography (3-5% MeOH in DCM) to give the title compound as a clear oil (111 mg, 47%). 1H NMR (500 MHz, CD3OD) δ ppm 7.28 (d, 1H, J=3.5 Hz), 7.14 (s, 1H), 6.47 (d, 1H, J=3.5 Hz), 4.89 (s, 4H), 4.33 (q, 1H, J=7.0 Hz), 4.10 (qAB, 4H, J=35.5, 7.5 Hz), 3.36 (s, 3H), 1.43 (d, 3H, J=7.0 Hz). ESI-MS m/z [M+H]+ calc'd for C15H20F4O, 273; found 273.

후처리

  1. temperaturecooled to 0° C.
  2. customquenched with MeOH (10 mL)
  3. waitAfter 10 minutes
  4. stirringThe reaction mixture was stirred for 20 minutes
  5. stirringthe reaction mixture was stirred for an additional 10 minutes
  6. dry with materialThe reaction mixture was dried over MgSO4
  7. filtrationfiltered through Celite
  8. concentrationconcentrated
  9. customThe crude product was purified by basic silica column chromatography (3-5% MeOH in DCM)

출처 및 근거

ORD 기록
ord-0505a6024c8a4371bc66a028d1f0ab44
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835420B2

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