Methanol → 1-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepin-9-yl)azetidin-3-ol

HRID 2044602Notes

Reaction equation

HRID 2044602 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21](O)[N:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].Cl.[OH:25][CH:26]1[CH2:29][NH:28][CH2:27]1.CCN(C(C)C)C(C)C.CO>C(Cl)Cl>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[N:20][C:21]([N:28]5[CH2:29][CH:26]([OH:25])[CH2:27]5)=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 1360309132-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-ol

Product 1

HCID 582043251-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepin-9-yl)azetidin-3-olYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Following the procedures of Example 339, 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-ol from Example 93 and 3-hydroxyazetidine hydrochloride with added DIPEA (2.2 eq.), were reacted and the crude product subjected to flash chromatography (SiO2, gradient 0 to 8% methanol in DCM) then recrystallisation from IMS to give 370 as pale green crystals (16 mg, 14%). LCMS: RT=2.26 min, [M+H]+ 368. 1H NMR 400 MHz (DMSO-d6) δ: 9.09 (1H, s), 7.90 (1H, d, J=0.63 Hz), 7.84 (1H, s), 5.95-5.94 (1H, m), 5.91 (1H, s), 5.70 (1H, d, J=6.40 Hz), 4.59 (1H, s), 4.55-4.47 (4H, m), 4.18 (2H, t, J=7.66 Hz), 3.70 (2H, dd, J=8.85, 4.66 Hz), 1.48 (6H, d, J=6.60 Hz)

Workup

  1. customwere reacted
  2. customrecrystallisation from IMS

Sources & evidence

ORD record
ord-dff8890d3dcf4d3e9486e1b42134165b
Source dataset
uspto-grants-2013_11
Patent number
US08586574B2

Reaction notes

Loading…