Methylamine → (+/-)-8-Fluoro-9-(3-hydroxy-3-methylcarbamoyl-but-1-ynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide

HRID 575081Notes

Reaction equation

HRID 575081 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[C:7]2=[CH:8][C:9]([C:19]#[C:20][C:21]([OH:27])([CH3:26])[C:22](OC)=[O:23])=[C:10]([F:18])[CH:11]=1)(=[O:3])[NH2:2].[CH3:28][NH2:29]>>[F:18][C:10]1[C:9]([C:19]#[C:20][C:21]([OH:27])([C:22](=[O:23])[NH:29][CH3:28])[CH3:26])=[CH:8][C:7]2[C:6]3[N:16]([CH2:15][CH2:14][O:13][C:12]=2[CH:11]=1)[CH:17]=[C:4]([C:1]([NH2:2])=[O:3])[N:5]=3

Participants

3

Reactant 2

HCID 6329MethylamineHCID 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 86693110(+/-)-8-Fluoro-9-(3-hydroxy-3-methylcarbamoyl-but-1-ynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide

Procedure

In a 20-mL sealed tube, methyl 4-[4-carbamoyl-12-fluoro-9-oxa-3,6-diazatricyclo[8.4.0.0[2,6]]tetradeca-1(14),2,4,10,12-pentaen-13-yl]-2-hydroxy-2-methylbut-3-ynoate (120 mg, 0.32 mmol, 1.00 equiv) was added into a solution of methanamine (30% w/w in ethanol, 5 mL). The resulting solution was stirred for 8 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 35 mg (29%) of 8-Fluoro-9-(3-hydroxy-3-methylcarbamoyl-but-1-ynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a yellow solid. LC-MS: (ES, m/z): 373 [M+H]; 1H-NMR: (300 MHz, DMSO-d6, ppm): δ 8.548 (d, 1H), 8.000-7.800 (m, 1H), 7.773 (s, 1H), 7.564 (br s, 1H), 7.108 (br s, 1H), 7.012 (d, 1H), 6.551 (s, 1H), 4.551-4.481 (m, 4H), 2.624 (d, 3H), 1.603 (s, 3H).

Workup

  1. customIn a 20-mL sealed tube
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThis resulted in 35 mg (29%) of 8-Fluoro-9-(3-hydroxy-3-methylcarbamoyl-but-1-ynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a yellow solid

Sources & evidence

ORD record
ord-4ae17d4f50384492991b25638930659c
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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