Methanol → HCID 68313041, compound

HRID 1530680Notes

Reaction equation

HRID 1530680 reaction equation
C(O1[CH2:12][CH2:11][CH:10]([N:13]2[C:17]([C:18]3[CH:19]=[C:20]4[C:29](=[CH:30][CH:31]=3)[C:28]3[N:24]([CH:25]=[C:26]([C:32]5[N:36]([CH2:37][CH:38]([O:40][CH3:41])[CH3:39])[N:35]=[CH:34][N:33]=5)[N:27]=3)[CH2:23][CH2:22][O:21]4)=[CH:16][CH:15]=[N:14]2)[CH2:9][CH2:8][NH:7][C:6]1=O)(C)(C)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].CO>C1COCC1>[CH3:41][O:40][CH:38]([CH3:39])[CH2:37][N:36]1[C:32]([C:26]2[N:27]=[C:28]3[C:29]4[CH:30]=[CH:31][C:18]([C:17]5[N:13]([CH:10]6[CH2:9][CH2:8][N:7]([CH3:6])[CH2:12][CH2:11]6)[N:14]=[CH:15][CH:16]=5)=[CH:19][C:20]=4[O:21][CH2:22][CH2:23][N:24]3[CH:25]=2)=[N:33][CH:34]=[N:35]1

Participants

5

Reactant 3

HCID 887MethanolHCID 21226445Aluminium lithium hydrideHCID 178495256HCID 178495256, compound

Product 1

HCID 68313041HCID 68313041, compoundYield 13.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-tert-butyl-6-(5-{4-[1-(2-methoxypropyl)-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)-1λ3,3-oxazocan-2-one (105 mg, 0.250 mmol) and LiAlH4 (51 mg, 1.3 mmol) in THF (5 mL) was refluxed for 1 hr. MeOH was added to quench reaction and the solid was filtered off. The filtrate was evaporated to afford the crude product, which was purified by preparative HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to give 267 (17 mg, 13% yield). LCMS (ESI): RT=4.80 min, m/z: 489.3 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 8.52 (d, J=8.5 Hz, 1H), 8.01 (s, 1H), 7.95 (s, 1H), 7.55 (d, J=1.5 Hz, 1H), 7.26-7.24 (m, 1H), 7.10 (d, J=1.5 Hz, 1H), 6.39 (d, J=1.5 Hz, 1H), 5.01-4.97 (m, 1H), 4.71-4.69 (m, 1H), 4.58 (t, J=13.5, 4H), 4.17-4.13 (m, 1H), 3.91-3.87 (m, 1H), 3.19 (s, 3H), 2.83 (d, J=12 Hz, 2H), 2.16-2.09 (m, 5H), 1.90 (t, J=53 Hz, 2H), 1.80 (d, J=11.5, 2H), 1.12 (d, J=6.5, 3H)

Workup

  1. temperaturewas refluxed for 1 hr
  2. customto quench
  3. customreaction
  4. filtrationthe solid was filtered off
  5. customThe filtrate was evaporated
  6. customto afford the crude product, which
  7. customwas purified by preparative 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-fd20e03c733d4ec38a2cd4607fb29d05
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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