Potassium Carbonate → HCID 68290775, compound

HRID 877765Notes

Reaction equation

HRID 877765 reaction equation
I.[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([CH2:17][CH3:18])[CH2:15][NH:14][CH2:13]3)=[C:9]([C:19]([NH2:21])=[O:20])[CH:8]=[N:7][N:6]2[CH:22]=1.BrC1C=C2C(Cl)=C(C(N)=O)C=NN2C=1.Cl[C:38]1[N:43]=[CH:42][C:41]([C:44]#[N:45])=[CH:40][N:39]=1.C(=O)([O-])[O-].[K+].[K+]>>[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([CH2:17][CH3:18])[CH2:15][N:14]([C:38]4[N:43]=[CH:42][C:41]([C:44]#[N:45])=[CH:40][N:39]=4)[CH2:13]3)=[C:9]([C:19]([NH2:21])=[O:20])[CH:8]=[N:7][N:6]2[CH:22]=1

Participants

5

Reactant 4

HCID 11430Potassium CarbonateHCID 214735922-Chloro-5-pyrimidinecarbonitrileHCID 682911926-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamideHCID 68291531HCID 68291531, compound

Product 1

HCID 68290775HCID 68290775, compoundYield 84%

Procedure

A mixture of 6-bromo-4-(((3S,4S)-4-ethylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide (0.250 g, 0.521 mmol, prepared from Intermediates 2 and 8 using the methods in Example 52 and Step 1 of Example 158), 2-chloropyrimidine-5-carbonitrile (0.087 g, 0.625 mmol), and potassium carbonate (0.216 g, 1.562 mmol) in a sealed vial was placed in a 90° C. heating block for 3 h. The mixture was triturated with water (5 mL). The resulting suspension was stirred for 10 min and filtered. The solid was washed with water (20 mL) and dried under vacuum to give 6-bromo-4-(((3S,4S)-1-(5-cyanopyrimidin-2-yl)-4-ethylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide as yellow solid (199 mg, 84% yield). 1H NMR (400 MHz, 1:1 mixture of chloroform-d/methanol-d4) δ ppm 8.57 (d, J=2.9 Hz, 1H), 8.51 (d, J=3.1 Hz, 1H), 8.11 (s, 1H), 7.64 (d, J=1.8 Hz, 1H), 6.92 (d, J=1.8 Hz, 1H), 4.89 (t, J=4.4 Hz, 1H), 4.18-4.01 (m, 2H), 4.00-3.88 (m, 1H), 3.52 (t, J=11.6 Hz, 1H), 2.71-2.50 (m, 1H), 1.85-1.68 (m, 2H), 1.05 (t, J=7.5 Hz, 3H); MS (ES+) m/z: 455.1 (M+H); LC retention time: 4.085 min (analytical HPLC Method H).

Workup

  1. customvial was placed in a 90° C.
  2. temperatureheating block for 3 h
  3. customThe mixture was triturated with water (5 mL)
  4. filtrationfiltered
  5. washThe solid was washed with water (20 mL)
  6. customdried under vacuum

Sources & evidence

ORD record
ord-877c523cabca44faaac4eec3442b5ca6
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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