Diisopropylethylamine → HCID 68292551, compound

HRID 1507968Notes

Reaction equation

HRID 1507968 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](Cl)=[C:8]([C:11]([NH2:13])=[O:12])[CH:7]=[N:6][N:5]2[CH:14]=1.Cl.[NH2:16][C@H:17]([CH3:23])[CH:18]([CH:20]1[CH2:22][CH2:21]1)[OH:19].CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:16][C@H:17]([CH3:23])[CH:18]([CH:20]3[CH2:22][CH2:21]3)[OH:19])=[C:8]([C:11]([NH2:13])=[O:12])[CH:7]=[N:6][N:5]2[CH:14]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 682911926-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamideHCID 86706850HCID 86706850, compound

Product 1

HCID 68292551HCID 68292551, compoundYield 30.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (272 mg, 0.989 mmol), (2R)-2-amino-1-cyclopropylpropan-1-ol hydrochloride (300 mg, 1.978 mmol) and DIPEA (0.691 ml, 3.96 mmol) were heated to 110° C. in NMP (3.297 ml) for 4 hrs. The reaction was then cooled to rt and ice-water added. After the ice had melted, the mixture was extracted with ethyl acetate (3×). The combined organics were then dried (MgSO4) and evaporated in vacuo before purifying by column chromatography using hexane ethyl acetate as eluent to give 6-bromo-4-(((2R)-1-cyclopropyl-1-hydroxypropan-2-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (111 mg, 0.299 mmol, 30.2% yield) as a mixture of diastereoisomers. 1H NMR (500 MHz, CCl3D) δ 7.93-7.78 (m, 1H), 7.68-7.52 (m, 1H), 6.93 (d, J=1.7 Hz, 1H), 5.44 (br. s., 1H), 4.53-4.27 (m, 1H), 4.13 (q, J=7.2 Hz, 1H), 2.99 (dd, J=9.2, 3.1 Hz, 1H), 1.48 (d, J=6.7 Hz, 3H), 1.27 (t, J=7.1 Hz, 2H), 1.14-0.99 (m, 1H), 0.65-0.53 (m, 2H), 0.43-0.27 (m, 2H).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×)
  2. dry with materialThe combined organics were then dried (MgSO4)
  3. customevaporated in vacuo
  4. custombefore purifying by column chromatography

Sources & evidence

ORD record
ord-24558c7443a642b7be6ce4b7502a5253
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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