Diisopropylethylamine → HCID 89995482, compound

HRID 1487337Notes

Reaction equation

HRID 1487337 reaction equation
[C:1]([C:3]1([C:6]([OH:8])=O)[CH2:5][CH2:4]1)#[N:2].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Br.[Br:46][C:47]1[N:48]=[C:49]2[C:54]([NH:55][C@H:56]3[C@@H:60]([CH3:61])[CH2:59][NH:58][CH2:57]3)=[C:53]([C:62]([NH2:64])=[O:63])[CH:52]=[N:51][N:50]2[CH:65]=1>C(Cl)Cl>[Br:46][C:47]1[N:48]=[C:49]2[C:54]([NH:55][C@H:56]3[C@@H:60]([CH3:61])[CH2:59][N:58]([C:6]([C:3]4([C:1]#[N:2])[CH2:5][CH2:4]4)=[O:8])[CH2:57]3)=[C:53]([C:62]([NH2:64])=[O:63])[CH:52]=[N:51][N:50]2[CH:65]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27332591-Cyanocyclopropanecarboxylic acidHCID 131736843HCID 131736843, compound

Product 1

HCID 89995482HCID 89995482, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-cyanocyclopropanecarboxylic acid (0.264 g, 2.380 mmol) in DCM (15.9 ml) were added DIEA (2.079 ml, 11.90 mmol), and BOP (1.263 g, 2.86 mmol). The solution was stirred at room temperature for 10 minutes, and 2-bromo-8-(((3S,4S)-4-methylpyrrolidin-3-yl)amino) imidazo[1,2-b]pyridazine-7-carboxamide, hydrobromide (from Step 2 of Example 1, 1.00 g, 2.380 mmol) was added. The reaction was stirred for 1 hr. After removal of the solvent, the crude product was purified by flash chromatography (ISCO, prepacked silica gel column eluting with 0-5% EtOAc/MeOH over 15 column volumes) to afford 2-bromo-8-(((3S,4S)-1-(1-cyanocyclopropanecarbonyl)-4-methylpyrrolidin-3-yl)amino)imidazo[1,2-b]pyridazine-7-carboxamide as a white solid, 1.01 g, 2.336 mmol, 98% yield. ESI-MS (Method B): m/z 434.1 ([M+H]+). HPLC (Method B) Rt: 2.505 min.

Workup

  1. stirringThe reaction was stirred for 1 hr
  2. customAfter removal of the solvent
  3. customthe crude product was purified by flash chromatography (ISCO, prepacked silica gel column eluting with 0-5% EtOAc/MeOH over 15 column volumes)

Sources & evidence

ORD record
ord-dbffa32ba54d44d2bac0ec02060b080a
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

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