Methanol → (2S)-4,4-difluoro-1-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepin-9-yl)pyrrolidine-2-carboxamide

HRID 1629431Notes

Reaction equation

HRID 1629431 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][C:6]([CH3:24])=[N:5]1)([CH3:3])[CH3:2].Cl.[F:26][C:27]1([F:35])[CH2:31][NH:30][C@H:29]([C:32]([NH2:34])=[O:33])[CH2:28]1.CO>C(Cl)Cl>[F:26][C:27]1([F:35])[CH2:31][N:30]([C:21]2[N:20]=[CH:19][C:16]3[C:17]4[N:11]([CH:10]=[C:9]([C:8]5[N:4]([CH:1]([CH3:2])[CH3:3])[N:5]=[C:6]([CH3:24])[N:7]=5)[N:18]=4)[CH2:12][CH2:13][O:14][C:15]=3[CH:22]=2)[C@H:29]([C:32]([NH2:34])=[O:33])[CH2:28]1

Participants

5

Reactant 3

HCID 887MethanolHCID 451589094,4-Difluoro-L-prolinamide hydrochlorideHCID 178432612HCID 178432612, compound

Product 1

HCID 58204575(2S)-4,4-difluoro-1-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepin-9-yl)pyrrolidine-2-carboxamideYield 17%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Following the procedures of Example 339, 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-ol and 4,4-difluoro-L-prolinamide hydrochloride with added TEA (2.5 eq.) were reacted and the crude product subjected to flash chromatography (SiO2, gradient 0 to 5% methanol in DCM) to give 383 as a white solid (29 mg, 17%). LCMS: RT=3.14 min, [M+H]+=459. 1H NMR 400 MHz (DMSO-d6) δ: 9.09 (1 H, s), 7.85 (1 H, d, J=0.64 Hz), 7.55 (1 H, br), 7.15 (1 H, br), 6.05 (1 H, s), 5.93-5.81 (1 H, m), 4.61 (1 H, dd, J=9.53, 4.24 Hz), 4.58-4.49 (4 H, m), 4.00-3.98 (2 H, m), 2.91-2.90 (1 H, m), 2.45 (1 H, dd, J=13.51, 4.18 Hz), 2.25 (3 H, s), 1.49 (6 H, dd, J=6.59, 3.35 Hz)

Workup

  1. customwere reacted

Sources & evidence

ORD record
ord-5e4cef7f703b4cb39f860a5fb2d5983c
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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