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 1530561Notes

Reaction equation

HRID 1530561 reaction equation
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]

Participants

5

Reactant 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

Product 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]oxazepineYield 27.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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)

Workup

  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)

Sources & evidence

ORD record
ord-457dac72979b4ba9ad0032275c9dd3bb
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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