Diisopropylethylamine → (2S,4S)-4-fluoro-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)pyrrolidine-2-carboxamide

HRID 886387Notes

Reaction equation

HRID 886387 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].[CH2:24]1[C@@H:28]([C:29]([NH2:31])=[O:30])[NH:27][CH2:26][C@H:25]1[F:32].Cl.CCN(C(C)C)C(C)C>>[F:32][C@@H:25]1[CH2:26][N:27]([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]=[CH:6][N:7]=5)[N:18]=4)[CH2:12][CH2:13][O:14][C:15]=3[CH:22]=2)[C@H:28]([C:29]([NH2:31])=[O:30])[CH2:24]1

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 451589172-Pyrrolidinecarboxamide, 4-fluoro-, hydrochloride (1:1), (2S,4S)-HCID 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 58204620(2S,4S)-4-fluoro-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)pyrrolidine-2-carboxamideYield 22%

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 4-cis-fluoro-L-prolinamide hydrochloride with added DIPEA (2.2 eq.), were reacted and the crude product recrystallised from IMS to give 373 as a white solid (56 mg, 22%). LCMS: RT=2.59 min, [M+H]+=427. 1H NMR 400 MHz (DMSO-d6) δ: 9.05 (1H, s), 7.84 (1H, d, J=0.63 Hz), 7.80 (1H, s), 7.11 (1H, s), 6.92 (1H, s), 5.93-5.91 (2H, m), 5.42 (1H, s), 5.29 (1H, s), 4.46-4.44 (5H, m), 3.83-3.54 (2H, m), 2.28 (1H, dd, J=20.28, 14.80 Hz), 1.43 (6H, dd, J=6.59, 3.60 Hz)

Workup

  1. customwere reacted
  2. customthe crude product recrystallised from IMS

Sources & evidence

ORD record
ord-1d89352a0319417c8684cc939f5eb568
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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