Hydrazine → HCID 69670263, compound

HRID 81069Notes

Reaction equation

C[N:2]=[C:3]=[O:4].[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:19]=[C:18](Cl)[C:15]([C:16]#[N:17])=[C:14]([C:21]3[CH:26]=[CH:25][C:24]([O:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:23][CH:22]=3)[N:13]=2)=[CH:8][CH:7]=1.[NH2:34][NH2:35].C[N:37](C)C(=O)C>C1COCC1.O.CO>[NH2:17][C:16]1[C:15]2[C:14]([C:21]3[CH:26]=[CH:25][C:24]([O:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:23][CH:22]=3)=[N:13][C:12]([C:9]3[CH:10]=[CH:11][C:6]([NH:5][C:3]([NH:2][NH2:37])=[O:4])=[CH:7][CH:8]=3)=[CH:19][C:18]=2[NH:35][N:34]=1

Participants

Conditions

Temperature: 150 °C

Procedure

Methyl isocyanate (1.4 mg, 0.025 mmol) was added to a solution of 6-(4-aminophenyl)-4-chloro-2-(4-phenoxyphenyl)nicotinonitrile (10 mg, 0.025 mmol, from Step 3 of Example 199) in THF (0.5 mL) at room temperature. After 18 h at room temperature, LCMS analysis showed that the first step was complete. The mixture was concentrated. The solid residue was treated with hydrazine (40 μL, 1.274 mmol) and N,N-dimethylacetamide (500 μL). The mixture was heated to 120° C. for 6 h and at 150° C. for 1 h. The crude material was diluted with water (0.5 mL) and methanol (1 mL) and purified by reverse phase HPLC (Sunfire S10 30×250 mm column), eluting with 40-70% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA). Example 203 was obtained as yellow solid (2.6 mg, 15% yield).

Workup

concentrationThe mixture was concentrated
custompurified by reverse phase HPLC (Sunfire S10 30×250 mm column)
washeluting with 40-70% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA)

Sources & evidence

ORD record: ord-4bdf2e1ddf16466b89527ef41f00eb4d
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846673B2

Reaction notes

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