Hydrazine → N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

HRID 1845440Notes

Reaction equation

HRID 1845440 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][C@@H:10]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)[CH2:11][N:12]2C(=O)C3C(=CC=CC=3)C2=O)=[O:8])=[CH:4][C:3]=1[C:31]1[N:35]([CH3:36])[N:34]=[CH:33][CH:32]=1.NN>O1CCCC1.CO>[NH2:12][CH2:11][C@@H:10]([NH:9][C:7]([C:5]1[S:6][C:2]([Cl:1])=[C:3]([C:31]2[N:35]([CH3:36])[N:34]=[CH:33][CH:32]=2)[CH:4]=1)=[O:8])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=1

Participants

5

Reactant 2

HCID 9321HydrazineHCID 578266985-chloro-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(3-fluorophenyl)methyl]ethyl}-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

Product 1

HCID 24996590N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 250 mL round-bottomed flask was added 5-chloro-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(3-fluorophenyl)methyl]ethyl}-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide (7.8 g, 14.91 mmol) and hydrazine (14.50 ml, 298 mmol) in tetrahydrofuran (THF) (75 ml) and methanol (75 mL). After 24 h at RT, the precipitate was filtered, the filtrate was concentrated. The crude product was purified on a silica gel column [CHCl3/MeOH/NH4OH, 90:9:1] to give the title compound as a white solid. The free base product was treated with 4M HCl in dioxane (15 mL). After 5 min, the solution was concentrated and dried under vacuum to afford the product (6.8 g, 95%) as an HCl salt: LCMS (ES) m/z 467 (M+H)+, 1H NMR (400 MHz, CD3OD) δ ppm 7.97 (s, 2H), 7.31 (s, 1H), 7.14 (m, 2H), 6.98 (m, 1H), 6.75 (s, 1H), 4.54 (m, 1H), 3.98 (s, 3H), 3.24 (m, 2H), 3.04 (m, 2H).

Workup

  1. filtrationthe precipitate was filtered
  2. concentrationthe filtrate was concentrated
  3. customThe crude product was purified on a silica gel column [CHCl3/MeOH/NH4OH, 90:9:1]

Sources & evidence

ORD record
ord-4112b7584fe44861a410aa5d4179a5f5
Source dataset
uspto-grants-2015_02
Patent number
US08946278B2

Reaction notes

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