Ammonia → 3-Amino-7-bromoisoquinoline-4-carbonitrile

HRID 1502237Notes

Reaction equation

HRID 1502237 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([CH2:8][NH2:9])[CH:7]=1.C(N(CC)C(C)C)(C)C.[C:20](#[N:24])[CH2:21][C:22]#[N:23].N>CN(C)C=O.CCOCC>[NH2:24][C:20]1[N:9]=[CH:8][C:6]2[C:5]([C:21]=1[C:22]#[N:23])=[CH:4][CH:3]=[C:2]([Br:1])[CH:7]=2

Participants

7

Reactant 4

HCID 222AmmoniaHCID 8010MalononitrileHCID 81531DiisopropylethylamineHCID 53401484(5-Bromo-2-iodophenyl)methanamine

Product 1

HCID 679748233-Amino-7-bromoisoquinoline-4-carbonitrileYield 62.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (5-bromo-2-iodophenyl)methanamine (40 g, 0.129 mol) in N,N-dimethylformamide (500 mL) was sequentially added N,N-diisopropylethylamine (33.3 g, 0.257 mol), malononitrile (16.9 g, 0.257 mol) and CuBr (36.9 g, 0.257 mol). The mixture was stirred at room temperature overnight. After that, to the reaction mixture was added ether and 10% NH3 (1 L, 1:1) and stirred at room temperature overnight open to the air. The mixture was separated and the residue was extracted with ethyl acetate three times, and the combined organic extracts were washed with brine, filtered, and evaporated to yield 20 g (62%) of 3-amino-7-bromoisoquinoline-4-carbonitrile. LCMS (ESI): M+H=247.7; 1H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.23 (d, J=2.0 Hz, 1H), 7.81 (dd, J=2.0, 9.2 Hz, 1H), 7.56 (d, J=9.2 Hz, 1H), 7.42 (s, 2H).

Workup

  1. stirringstirred at room temperature overnight open to the air
  2. customThe mixture was separated
  3. extractionthe residue was extracted with ethyl acetate three times
  4. washthe combined organic extracts were washed with brine
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-460d1d54692a426db26edbd2824cd056
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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