Ammonia → ethyl 3-((1-(1-(2-(carbamoyloxy)ethyl)-1H-pyrazol-4-yl)-6-chloro-2-cyclopropyl-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate

HRID 522782Notes

Reaction equation

HRID 522782 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:23][C:24]3[C:25]([F:35])=[C:26]([CH:32]=[CH:33][CH:34]=3)[C:27]([O:29][CH2:30][CH3:31])=[O:28])=[C:7]([CH:20]3[CH2:22][CH2:21]3)[N:8]2[C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18][OH:19])[CH:16]=2)=[CH:4][CH:3]=1.[NH3:36].C1[CH2:41][O:40]CC1>>[C:41]([O:19][CH2:18][CH2:17][N:15]1[CH:16]=[C:12]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[C:10]=3[F:11])[C:6]([S:23][C:24]3[C:25]([F:35])=[C:26]([CH:32]=[CH:33][CH:34]=3)[C:27]([O:29][CH2:30][CH3:31])=[O:28])=[C:7]2[CH:20]2[CH2:22][CH2:21]2)[CH:13]=[N:14]1)(=[O:40])[NH2:36]

Participants

4

Reactant 3

HCID 222AmmoniaHCID 8028TetrahydrofuranHCID 118104210ethyl 3-((6-chloro-2-cyclopropyl-7-fluoro-1-(1-(2-hydroxvethyl)-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)-2-fluorobenzoate

Product 1

HCID 118104209ethyl 3-((1-(1-(2-(carbamoyloxy)ethyl)-1H-pyrazol-4-yl)-6-chloro-2-cyclopropyl-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoateYield 35%

Procedure

To a stirred solution of compound 2 (20 mg, 0.031 mmol) in THF (3 mL) under inert atmosphere was passed ammonia gas at 0° C. for 15 min; warmed to RT and stirred for 30 min. The volatiles were removed under reduced pressure and the crude was purified by triturating with n-pentane (2×5 mL) and dried under reduced pressure to afford 3 (6 mg, 35%) as a pale brown oil. 1H NMR (500 MHz, CDCl3): δ 7.73 (s, 1H), 7.70 (s, 1H), 7.64 (t, J=8.0 Hz, 1H), 7.20 (d, J=8.5 Hz, 1H), 7.11-7.08 (m, 1H), 6.95 (t, J=8.0 Hz, 1H), 6.79 (t, J=8.0 Hz, 1H), 4.65 (br s, 2H), 4.54-4.47 (m, 4H), 4.42 (q, 2H), 1.74-1.70 (m, 1H), 1.43 (t, J=7.5 Hz, 3H), 1.07-1.05 (m, 2H), 0.91-0.88 (m, 2H); LC-MS: m/z 561.7 (M+H+).

Workup

  1. customat 0° C.
  2. customfor 15 min
  3. customThe volatiles were removed under reduced pressure
  4. customthe crude was purified
  5. customby triturating with n-pentane (2×5 mL)
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-a5ac740ed2d64a5685afd037b25374cd
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

Loading…