Glycinamide hydrochloride → 2-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepin-9-ylamino)acetamide

HRID 1629444Notes

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.[NH2:25][CH2:26][C:27]([NH2:29])=[O:28]>CN1C(=O)CCC1>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[N:20][C:21]([NH:25][CH2:26][C:27]([NH2:29])=[O:28])=[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

Conditions

Temperature: 85 °C

Procedure

Following the procedure for 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 glycinamide hydrochloride salt in NMP were heated at 85° C. for 20 h. The reaction mixture was cooled and loaded onto an Isolute SCX-2 cartridge, washed with methanol and eluted with 2M ammonia in methanol and appropriate fractions concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% 2M ammonia in methanol in DCM). The solid was recrystallised from methanol to give 404 as a white solid (19 mg, 8%). LCMS: RT=2.14 min, [M+H]+=369. 1H NMR 400 MHz (DMSO-d6) δ: 9.01 (1 H, s), 7.90 (1 H, d, J=0.63 Hz), 7.82 (1 H, s), 7.32 (1 H, br, s), 7.01 (1 H, br, s), 6.11 (1 H, s), 5.97-5.88 (1 H, m), 4.49-4.48 (4 H, m), 3.84 (2 H, d, J=4.26 Hz), 1.48 (6 H, d, J=6.60 Hz)

Workup

temperatureThe reaction mixture was cooled
washwashed with methanol
washeluted with 2M ammonia in methanol and appropriate fractions
concentrationconcentrated in vacuo
customThe solid was recrystallised from methanol

Sources & evidence

ORD record: ord-aa0946f39f2e409997ae55a08490188b
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785626B2

Reaction notes

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