Ammonia → (1aR,5aR)-2-(2,4-Difluoro-phenyl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic Acid Amide

HRID 1623912Notes

Reaction equation

HRID 1623912 reaction equation
C([O:3][C:4]([C:6]1[C:7]2[CH2:8][C@H:9]3[CH2:22][C@H:10]3[C:11]=2[N:12]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[N:13]=1)=O)C.[NH3:23]>>[F:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=1[N:12]1[C:11]2[C@@H:10]3[CH2:22][C@@H:9]3[CH2:8][C:7]=2[C:6]([C:4]([NH2:23])=[O:3])=[N:13]1

Participants

3

Reactant 2

HCID 222AmmoniaHCID 68182446(1aR,5aR)-2-(2,4-difluoro-phenyl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester

Product 1

HCID 68182363(1aR,5aR)-2-(2,4-Difluoro-phenyl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic Acid AmideYield 67.5%

Conditions

Temperature
100 °C

Procedure

(1aR,5aR)-2-(2,4-Difluoro-phenyl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester (200 mg, 0.657 mmol) was partially dissolved in a 7 M methanolic solution of ammonia (2 mL, 14.00 mmol). The mixture was heated under microwave irradiation in a sealed, thick-walled glass tube for 1 h at 100° C., then 2 h at 120° C. and 12 h at 125° C. The methanol was removed under reduced pressure. The remaining residue was triturated with ether and the precipitate was collected by filtration to give the title compound (122 mg) as a tan solid. LCMS m/z=276.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.40 (td, J=4.4, 3.4 Hz, 1H), 1.15 (td, J=7.8, 4.7 Hz, 1H), 2.15-2.20 (m, 1H), 2.23-2.30 (m, 1H), 2.77 (d, J=16.7 Hz, 1H), 2.89 (dd, J=16.4, 6.4 Hz, 1H), 7.22 (bs, 1H), 7.28-7.33 (m, 1H), 7.35 (bs, 1H), 7.56-7.62 (m, 1H), 7.77 (td, J=8.9, 6.0 Hz, 1H).

Workup

  1. custom2 h
  2. customat 120° C.
  3. custom12 h
  4. customat 125° C
  5. customThe methanol was removed under reduced pressure
  6. customThe remaining residue was triturated with ether
  7. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-77148c611b4742698a69c3a11f2e884c
Source dataset
uspto-grants-2014_07
Patent number
US08778950B2

Reaction notes

Loading…