Triethylamine → 10-(4-(3-Cyanoazetidin-1-yl)-3-hydroxy-3-methyl-4-oxobut-1-yn-1-yl)-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

HRID 575080Notes

Reaction equation

HRID 575080 reaction equation
[C:1]([C:4]1[N:5]=[C:6]2[N:16]([CH:17]=1)[CH2:15][CH2:14][O:13][C:12]1[CH:11]=[C:10]([F:18])[C:9]([C:19]#[C:20][C:21]([OH:27])([CH3:26])[C:22](OC)=[O:23])=[CH:8][C:7]2=1)(=[O:3])[NH2:2].Cl.[NH:29]1[CH2:32][CH:31]([C:33]#[N:34])[CH2:30]1.C(N(CC)CC)C>CO>[C:33]([CH:31]1[CH2:32][N:29]([C:22](=[O:23])[C:21]([OH:27])([CH3:26])[C:20]#[C:19][C:9]2[C:10]([F:18])=[CH:11][C:12]3[O:13][CH2:14][CH2:15][N:16]4[C:6](=[N:5][C:4]([C:1]([NH2:2])=[O:3])=[CH:17]4)[C:7]=3[CH:8]=2)[CH2:30]1)#[N:34]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 45072465Azetidine-3-carbonitrile hydrochlorideHCID 86693109Methyl 4-(2-carbamoyl-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-10-yl)-2-hydroxy-2-methylbut-3-ynoate

Product 1

HCID 8669310810-(4-(3-Cyanoazetidin-1-yl)-3-hydroxy-3-methyl-4-oxobut-1-yn-1-yl)-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

Into a 10-mL sealed tube, was placed a solution of methyl 4-[4-carbamoyl-12-fluoro-9-oxa-3,6-diazatricyclo[8.4.0.0[2,6]]tetradeca-1(10),2,4,11,13-pentaen-13-yl]-2-hydroxy-2-methylbut-3-ynoate (150 mg, 0.40 mmol, 1.00 equiv), azetidine-3-carbonitrile hydrochloride (237 mg, 2.00 mmol, 5.00 equiv), triethylamine (203 mg, 2.01 mmol, 5.00 equiv) in methanol (5 mL). The resulting solution was stirred for 12 h at 40° C. in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (30:1). This resulted in 8.8 mg (5%) of 9-[4-(3-Cyano-azetidin-1-yl)-3-hydroxy-3-methyl-4-oxo-but-1-ynyl]-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a off-white solid. LC-MS: (ES, m/z): 424 [M+H]+1H-NMR: (300 MHz, DMSO-d6, ppm): δ 8.594 (d, 1H), 7.785 (s, 1H), 7.562 (d, 1H), 7.145 (s, 1H), 7.062 (d, 1H), 6.438 (d, 1H), 4.748 (t, 1H), 4.600-4.410 (m, 5H), 4.300-4.190 (m, 1H), 4.180-4.000 (m, 1H), 3.900-3.710 (m, 1H), 1.610 (s, 3H).

Workup

  1. customInto a 10-mL sealed tube
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThis resulted in 8.8 mg (5%) of 9-[4-(3-Cyano-azetidin-1-yl)-3-hydroxy-3-methyl-4-oxo-but-1-ynyl]-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a off-white solid

Sources & evidence

ORD record
ord-7e38bef51b6446daba5ad5889ed8b41e
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

Loading…