HCID 3297125, compound → HCID 66558676, compound

HRID 1530608Notes

Reaction equation

HRID 1530608 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:15]4[N:16]([CH:21]([CH3:23])[CH3:22])[N:17]=[C:18]([CH3:20])[N:19]=4)=[CH:10]3)[C:6]=2[CH:24]=1.[CH3:25][N:26]1[CH2:31][CH2:30][CH:29]([CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][NH:33]2)[CH2:28][CH2:27]1.CC(C)([O-])C.[Na+]>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:21]([N:16]1[C:15]([C:9]2[N:8]=[C:7]3[C:6]4[CH:24]=[CH:2][C:3]([N:33]5[CH2:34][CH2:35][CH2:36][CH2:37][CH:32]5[CH:29]5[CH2:28][CH2:27][N:26]([CH3:25])[CH2:31][CH2:30]5)=[CH:4][C:5]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:19][C:18]([CH3:20])=[N:17]1)([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 3297125HCID 3297125, compoundHCID 23676156Sodium t-butoxideHCID 5820476010-bromo-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 66558676HCID 66558676, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 9-bromo-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene from Example 6 (200 mg, 0.51 mmol), l′-methyl-[2,4]bipiperidinyl (234 mg, 1.28 mmol), sodium tertbutoxide (148 mg, 1.5 mmol) and Pd(P(tBu)3)2 (13 mg, 0.026 mmol) in dioxane was degassed with a stream of argon and then heated at 100° C. for 1 h in a sealed tube. After cooling to RT, the mixture was diluted with water and extracted with EtOAc (×3). The combined organic phases were concentrated in vacuo and then purified by column chromatography (Si-PCC, gradient 0-10% MeOH in EtOAc, and then with 20% 2M NH3/MeOH in DCM) followed by HPLC purification (Phenomenex Gemini 5 μm C18 on a 25 min gradient 50-95% 0.1% NH4OH in acetonitrile/water) affording 215 (30 mg, 12%). LCMS: RT 2.98 min [M+H]+ 490.2. 1H NMR (CDCl3, 400 MHz): δ 8.27 (1H, d, J=8.98 Hz), 7.51 (1H, s), 6.63 (1H, dd, J=9.25, 2.95 Hz), 6.38 (1H, d J=2.95 Hz), 6.00-5.88 (1H, m), 4.46-4.39 (2H, m), 4.38-4.30 (2H, m), 3.68-3.59 (2H, m), 3.11-3.02 (1H, m), 2.95-2.88 (1H, m), 2.85-2.78 (1H, m), 2.4 (3H, s), 2.25 (3H, s), 1.98-1.60 (11H, m), 1.56 (6H, d, J=7.15 Hz), 1.40-1.19 (2H, m)

Workup

  1. customwas degassed with a stream of argon
  2. temperatureAfter cooling to RT
  3. additionthe mixture was diluted with water
  4. extractionextracted with EtOAc (×3)
  5. concentrationThe combined organic phases were concentrated in vacuo
  6. custompurified by column chromatography (Si-PCC, gradient 0-10% MeOH in EtOAc
  7. customwith 20% 2M NH3/MeOH in DCM) followed by HPLC purification (Phenomenex Gemini 5 μm C18 on a 25 min gradient 50-95% 0.1% NH4OH in acetonitrile/water)

Sources & evidence

ORD record
ord-06437c5b239b47e5964e88abe2c5fe08
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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