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

HRID 575085Notes

Reaction equation

HRID 575085 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].[NH3:28].CO>>[C:22]([C:21]([OH:27])([CH3:26])[C:20]#[C:19][C:9]1[C:10]([F:18])=[CH:11][C:12]2[O:13][CH2:14][CH2:15][N:16]3[C:6](=[N:5][C:4]([C:1]([NH2:2])=[O:3])=[CH:17]3)[C:7]=2[CH:8]=1)(=[O:23])[NH2:28]

Participants

3

Reactant 2

HCID 21705897Ammonia methanolHCID 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 71715163(+/-)-9-(3-Carbamoyl-3-hydroxy-but-1-ynyl)-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide

Conditions

Temperature
25 °C

Procedure

Into a 100-mL round-bottom flask, was placed a solution of 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 (300 mg, 0.80 mmol, 1.00 equiv) in NH3/MeOH (30 w/w %, 40 mL). The resulting solution was stirred for 12 h at 25° C. The resulting mixture was concentrated under vacuum. The resulting mixture was washed with 3×10 mL of methanol and 2×5 mL of CH3CN. The trace solvents were removed under reduced pressure. This resulted in 43 mg (15%) of 9-(3-Carbamoyl-3-hydroxy-but-1-ynyl)-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a brown solid. LC-MS: (ES, m/z): 359[M+H]+; 1H-NMR: (400 MHz, DMSO-d6, ppm): δ 8.579 (d, 1H), 7.786 (s, 1H), 7.589 (br s, 1H), 7.378 (br s, 2H), 7.128 (br s, 1H), 7.029 (d, 1H), 6.423 (s, 1H), 4.600-4.410 (m, 4H), 1.612 (s, 3H).

Workup

  1. customInto a 100-mL round-bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. washThe resulting mixture was washed with 3×10 mL of methanol and 2×5 mL of CH3CN
  4. customThe trace solvents were removed under reduced pressure
  5. customThis resulted in 43 mg (15%) of 9-(3-Carbamoyl-3-hydroxy-but-1-ynyl)-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a brown solid

Sources & evidence

ORD record
ord-1d56c945b98f491a81e22e2339b9d351
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

Loading…