Water → 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-9-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530561ノート

反応式

HRID 1530561 の反応式
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]([C:19]3[CH:20]=[C:21]4[C:30](=[CH:31][CH:32]=3)[C:29]3[N:25]([CH:26]=[C:27]([C:33]5[N:37]([CH:38]([CH3:40])[CH3:39])[N:36]=[CH:35][N:34]=5)[N:28]=3)[CH2:24][CH2:23][O:22]4)=[CH:17][CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].O>C1COCC1>[CH:38]([N:37]1[C:33]([C:27]2[N:28]=[C:29]3[C:30]4[CH:31]=[CH:32][C:19]([C:18]5[N:14]([CH:11]6[CH2:12][CH2:13][N:8]([CH3:6])[CH2:9][CH2:10]6)[N:15]=[CH:16][CH:17]=5)=[CH:20][C:21]=4[O:22][CH2:23][CH2:24][N:25]3[CH:26]=2)=[N:34][CH:35]=[N:36]1)([CH3:40])[CH3:39]

参加物

5

反応物 3

HCID 962WaterHCID 21226445Aluminium lithium hydrideHCID 68313074tert-butyl-4-(5-{4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-1-yl)piperidine-1-carboxylate

生成物 1

HCID 665587572-(1-isopropyl-1H-1,2,4-triazol-5-yl)-9-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine収率 27.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of tert-butyl-4-(5-{4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-1-yl)piperidine-1-carboxylate (100 mg, 0.184 mmol) and LiAlH4 (35.0 mg, 0.921 mmol) in THF (5.00 mL) was refluxed for 1 h. At the end of reaction, H2O was added to quench reaction. After filtration, the filtrate was evaporated to afford the crude product, which was purified by reverse phase combiflash eluting with 0-50% gradient CH3CN in 0.5% NH4HCO3 and followed by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to give 160 (23 mg, 27% yield) as white solid. LCMS (ESI): RT=4.93 min, m/z: 459.4 [M+H+]. 1H-NMR (500 MHz, DMSO-d6): δ 8.53 (d, J=8.5 Hz, 1H), 7.99 (s, 1H), 7.93 (s, 1H), 7.55 (d, J=1.5 Hz, 1H), 7.24 (d, J=8.0 Hz, 1H), 7.10 (s, 1H), 6.39 (d, J=1.5 Hz, 1H), 5.94-5.91 (m, 1H), 4.57 (s, 4H), 4.15 (s, 1H), 2.84-2.82 (m, 2H), 2.16 (s, 3H), 2.15-2.12 (m, 2H), 1.94-1.89 (m, 2H), 1.10-1.79 (m, 2H), 1.50 (s, 6H)

後処理

  1. temperaturewas refluxed for 1 h
  2. additionwas added
  3. customto quench
  4. customreaction
  5. filtrationAfter filtration
  6. customthe filtrate was evaporated
  7. customto afford the crude product, which
  8. customwas purified by reverse phase combiflash
  9. washeluting with 0-50% gradient CH3CN in 0.5% NH4HCO3
  10. customfollowed by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

出典と根拠

ORDレコード
ord-457dac72979b4ba9ad0032275c9dd3bb
出典データセット
uspto-grants-2015_07
特許番号
US09090628B2

反応ノート

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