Water → 2-(3-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1-methyl-1H-pyrazol-5-yl)piperidin-1-yl)-2-methylpropan-1-ol

HRID 1530637Notes

Reaction equation

HRID 1530637 reaction equation
[CH3:1][C:2]([N:9]1[CH2:14][CH2:13][CH2:12][CH:11]([C:15]2[N:19]([CH3:20])[N:18]=[CH:17][C:16]=2[C:21]2[CH:22]=[C:23]3[C:32](=[CH:33][CH:34]=2)[C:31]2[N:27]([CH:28]=[C:29]([C:35]4[N:39]([CH:40]([CH3:42])[CH3:41])[N:38]=[C:37]([CH3:43])[N:36]=4)[N:30]=2)[CH2:26][CH2:25][O:24]3)[CH2:10]1)([CH3:8])[C:3](OCC)=[O:4].[H-].[H-].[H-].[H-].[Li+].[Al+3].O>C1COCC1>[CH:40]([N:39]1[C:35]([C:29]2[N:30]=[C:31]3[C:32]4[CH:33]=[CH:34][C:21]([C:16]5[CH:17]=[N:18][N:19]([CH3:20])[C:15]=5[CH:11]5[CH2:12][CH2:13][CH2:14][N:9]([C:2]([CH3:1])([CH3:8])[CH2:3][OH:4])[CH2:10]5)=[CH:22][C:23]=4[O:24][CH2:25][CH2:26][N:27]3[CH:28]=2)=[N:36][C:37]([CH3:43])=[N:38]1)([CH3:42])[CH3:41]

Participants

5

Reactant 3

HCID 962WaterHCID 21226445Aluminium lithium hydrideHCID 68312948ethyl 2-methyl-2-[3-(1-methyl-4-{4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-5-yl)piperidin-1-yl]propanoate

Product 1

HCID 665589202-(3-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1-methyl-1H-pyrazol-5-yl)piperidin-1-yl)-2-methylpropan-1-olYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 2-methyl-2-[3-(1-methyl-4-{4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-5-yl)piperidin-1-yl]propanoate (35 mg, 0.060 mmol) in dry THF (2 ml), was added LiAlH4 (11.4 mg, 0.300 mmol) in small portions at room temperature. The resulting mixture was heated to reflux for 1 h. Water (1 mL) was added to quench the reaction. The organic layer was separated, dried over Na2SO4, and concentrated. The residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford 248 (10 mg, 31% yield). LCMS (ESI): RT=4.72 min, m/z: 545.4 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 8.39 (d, J=8.5 Hz, 1H), 7.91 (s, 1H), 7.43 (s, 1H), 7.09-7.08 (m, 1H), 6.93 (d, J=1.5 Hz, 1H), 5.86-5.83 (m, 1H), 4.53 (d, J=6.0 Hz, 4H), 4.27-4.25 (m, 1H), 3.89 (s, 3H), 3.28-3.25 (m, 2H), 2.99-2.96 (m, 3H), 2.44-2.40 (m, 2H), 2.26 (s, 3H), 2.08-2.06 (m, 1H), 1.58-1.70 (m, 3H), 1.47-1.45 (m, 6H), 0.93-0.91 (m, 6H)

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 1 h
  3. customto quench
  4. customthe reaction
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified 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-d4092e5cac464fa58daaedb991d08e32
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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