Sodium Bicarbonate → 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-N-(1-isopropylazetidin-3-yl)-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine-9-carboxamide

HRID 1799992Notes

Reaction equation

HRID 1799992 reaction equation
[NH:1]1[CH2:4][CH:3]([NH:5][C:6]([C:8]2[CH:9]=[CH:10][C:11]3[O:20][CH2:19][CH2:18][C:17]4[N:13]([N:14]=[C:15]([C:21]5[N:22]([CH:26]([CH3:28])[CH3:27])[N:23]=[CH:24][N:25]=5)[CH:16]=4)[C:12]=3[CH:29]=2)=[O:7])[CH2:2]1.C(O[BH-](O[C:40](=O)[CH3:41])OC(=O)C)(=O)C.[Na+].[C:44](=O)([O-])O.[Na+]>CC(C)=O.C(Cl)Cl.CO.C(O)(=O)C>[CH:26]([N:22]1[C:21]([C:15]2[CH:16]=[C:17]3[N:13]([C:12]4[CH:29]=[C:8]([C:6]([NH:5][CH:3]5[CH2:2][N:1]([CH:40]([CH3:41])[CH3:44])[CH2:4]5)=[O:7])[CH:9]=[CH:10][C:11]=4[O:20][CH2:19][CH2:18]3)[N:14]=2)=[N:25][CH:24]=[N:23]1)([CH3:27])[CH3:28]

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 670506702-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene-9-carboxylic acid azetidin-3-ylamide

Product 1

HCID 683553452-(1-isopropyl-1H-1,2,4-triazol-5-yl)-N-(1-isopropylazetidin-3-yl)-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine-9-carboxamide

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 180AcetoneSolvent2×HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene-9-carboxylic acid azetidin-3-ylamide (0.15 g, 0.38 mmol), acetone (84 L, 1.14 mmol), acetic acid (22 L), methanol (1 mL) and DCM (1 mL) was stirred at RT for 1 h. Sodium triacetoxyborohydride (0.2 g, 0.95 mmol) was added and the resultant mixture stirred at RT for 72 h. Further acetone (84 L) and 4 Å molecular sieves were added then stirring continued for 1 h before the addition of further sodium triacetoxyborohydride (0.2 g, 0.95 mmol). The reaction mixture was stirred at RT for 18 h before the addition of saturated aqueous sodium hydrogen carbonate. The resultant mixture was extracted with 10% MeOH in DCM. The combined extracts were dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% MeOH in DCM) followed by trituration in diethyl ether and recrystallisation in ethyl acetate to give 167 as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.47 (d, J=2.22 Hz, 1H); 7.95 (s, 1H); 7.71 (dd, J=8.44, 2.24 Hz, 1H); 7.23 (d, J=8.43 Hz, 1H); 6.87 (s, 1 H); 5.72-5.64 (m, 1H); 4.74-4.67 (m, 1H); 4.58 (t, J=5.67 Hz, 2H); 3.68 (t, J=7.42 Hz, 2H); 3.22 (t, J=5.69 Hz, 2H); 3.12 (s, 2H); 2.38 (t, J=7.02 Hz, 1H); 1.61 (d, J=6.61 Hz, 6H); 0.98 (d, J=6.21 Hz, 6H). LCMS: RT=6.82 min, M+H+=436

Workup

  1. extractionThe resultant mixture was extracted with 10% MeOH in DCM
  2. dry with materialThe combined extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customrecrystallisation in ethyl acetate

Sources & evidence

ORD record
ord-175fcc5a77d3438e861d12b66a4aaa9b
Source dataset
uspto-grants-2013_01
Patent number
US08343955B2

Reaction notes

Loading…