Potassium Carbonate → 2-(4-(2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepin-9-yl)piperidin-1-yl)acetamide

HRID 886147Notes

Reaction equation

HRID 886147 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:8]=[CH:9][C:10]3[O:19][CH2:18][CH2:17][C:16]4[N:12]([N:13]=[C:14]([C:20]5[N:21]([CH2:25][C:26]([F:29])([F:28])[F:27])[N:22]=[CH:23][N:24]=5)[CH:15]=4)[C:11]=3[CH:30]=2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:38][C:39]([NH2:41])=[O:40]>CN(C=O)C>[F:28][C:26]([F:29])([F:27])[CH2:25][N:21]1[C:20]([C:14]2[CH:15]=[C:16]3[N:12]([C:11]4[CH:30]=[C:7]([CH:4]5[CH2:3][CH2:2][N:1]([CH2:38][C:39]([NH2:41])=[O:40])[CH2:6][CH2:5]5)[CH:8]=[CH:9][C:10]=4[O:19][CH2:18][CH2:17]3)[N:13]=2)=[N:24][CH:23]=[N:22]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 696322-BromoacetamideHCID 582048839-(piperidin-4-yl)-2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine

Product 1

HCID 582049682-(4-(2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepin-9-yl)piperidin-1-yl)acetamideYield 56.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 9-piperidin-4-yl-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene (180 mg, 0.43 mmol) in DMF (1 mL) was treated with potassium carbonate (89 mg, 0.65 mmol) and bromo acetamide (77 mg, 0.56 mmol) and then stirred at RT for 18 h. The reaction mixture was partitioned between ethyl acetate and water, the aqueous layer extracted with ethyl acetate and the combined organic extracts dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was triturated in diethyl ether to give 143 as a pale yellow solid (115 mg, 54%). 1H NMR (DMSO-d6, 400 MHz): δ 8.21 (s, 1H); 7.75 (d, J=2.2 Hz, 1H); 7.28 (dd, J=8.4, 2.2 Hz, 1H); 7.20 (d, J=8.3 Hz, 1H); 7.15 (s, 2H); 6.97 (s, 1H); 5.73 (q, J=8.8 Hz, 2H); 4.49 (t, J=6.0 Hz, 2H); 3.20 (t, J=6.0 Hz, 2H); 2.96-2.85 (m, 4H); 2.62-2.52 (m, 1H); 2.24-2.14 (m, 2H); 1.84-1.66 (m, 4H). LCMS: RT=6.55 min, M+H+=476

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. extractionthe aqueous layer extracted with ethyl acetate
  3. dry with materialthe combined organic extracts dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was triturated in diethyl ether

Sources & evidence

ORD record
ord-4e62a534ab3d4364b13228fe59cf48d7
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

Loading…