Dichloromethane → HCID 59471825, compound

HRID 78653Notes

Reaction equation

HRID 78653 reaction equation
O.NN.[NH2:4][C:5]1[C:6]([C:23]2[O:27][C:26]([NH:28][C:29](=[O:42])[CH2:30][N:31]3C(=O)C4C(=CC=CC=4)C3=O)=[N:25][N:24]=2)=[N:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH:20]([CH3:22])[CH3:21])(=[O:19])=[O:18])=[CH:13][CH:12]=2)=[CH:9][N:10]=1.C(Cl)Cl>CO>[NH2:31][CH2:30][C:29]([NH:28][C:26]1[O:27][C:23]([C:6]2[C:5]([NH2:4])=[N:10][CH:9]=[C:8]([C:11]3[CH:12]=[CH:13][C:14]([S:17]([CH:20]([CH3:22])[CH3:21])(=[O:18])=[O:19])=[CH:15][CH:16]=3)[N:7]=2)=[N:24][N:25]=1)=[O:42]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 24654Hydrazine hydrate (1:1)2×HCID 59472311HCID 59472311, compound

Product 1

HCID 59471825HCID 59471825, compoundYield 14.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Hydrazine hydrate (8.065 mg, 7.838 μL, 0.1611 mmol) was added to a stirred suspension of N-(5-(3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)-2-(1,3-dioxoisoindolin-2-yl)acetamide (147 mg, 0.1611 mmol) in MeOH (5 mL)/CH2Cl2 (5 mL) and the reaction mixture was allowed to stir at ambient temperature for 2 hours. A further portion of hydrazine hydrate (16.13 mg, 15.68 μL, 0.3222 mmol) was added and the reaction stirred for a further 16 hours. The solvent was removed in vacuo and residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3 CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound as a yellow solid (10 mg, 11%); 1H NMR (400.0 MHz, DMSO) d 1.18 (d, 6H), 3.50-3.53 (m, 1H), 4.11 (s, 1.4H), 4.33 (s, 0.6H), 7.81 (s, 2H), 7.91 (d, 2H), 8.53 (d, 2H), 9.07 (s, 1H), 10.99 (s, 0.7H) and 11.16 (s, 0.3H) ppm; MS (ES+) 418.2

Workup

  1. stirringthe reaction stirred for a further 16 hours
  2. customThe solvent was removed in vacuo and residue
  3. customwas purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3 CN) over 16 minutes at 25 mL/min]
  4. customThe fractions were collected
  5. customfreeze-dried

Sources & evidence

ORD record
ord-53170f6260e54cc1b24047264a79b042
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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