Hydrazine hydrate (1:1) → 6-(3-Amino-1H-indazol-6-yl)-N4-[(2-chlorophenyl)methyl]-2,4-pyrimidinediamine

HRID 2367245Notes

Reaction equation

HRID 2367245 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([NH:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])[N:3]=1.O.[NH2:27][NH2:28]>C(O)C>[NH2:13][C:12]1[C:11]2[C:10](=[CH:9][C:8]([C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([NH:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[Cl:25])[CH:5]=3)=[CH:15][CH:14]=2)[NH:28][N:27]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 669909474-(2-Amino-6-{[(2-chlorophenyl)methyl]amino}-4-pyrimidinyl)-2-fluorobenzonitrile

Product 1

HCID 462164896-(3-Amino-1H-indazol-6-yl)-N4-[(2-chlorophenyl)methyl]-2,4-pyrimidinediamineYield 18.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To 4-(2-amino-6-{[(2-chlorophenyl)methyl]amino}-4-pyrimidinyl)-2-fluorobenzonitrile (800 mg, 2.27 mmol) in ethanol (2 mL) was added hydrazine monohydrate (3 mL, 74 mmol), and the reaction mixture was heated to 100° C. for 1 hour in a BiotageInitiator® microwave synthesizer. Upon cooling, the reaction mixture was concentrated in vacuum and purified by RPHPLC (BiotageSP1) (gradient: 30% CH3CN/H2O to 60% CH3CN/H2O) to afford the title compound (151 mg) as an off-white solid. LC-MS (ES) m/z=366 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 4.61 (d, J=5.6 Hz, 2H), 5.37 (s, 2H), 6.07 (s, 2H), 6.40 (s, 1H), 7.34-7.27 (m, 2H), 7.46-7.41 (m, 4H), 7.70 (d, J=8.8 Hz, 1H), 7.84 (s, 1H), 11.52 (s, 1H).

Workup

  1. temperatureUpon cooling
  2. concentrationthe reaction mixture was concentrated in vacuum
  3. custompurified by RPHPLC (BiotageSP1) (gradient: 30% CH3CN/H2O to 60% CH3CN/H2O)

Sources & evidence

ORD record
ord-c3e7a36c0fc44b20b06e9d1ce08fbbc1
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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