Acetic Acid → tert-Butyl 4-(5-(8-morpholino-2-((quinolin-2-ylamino)methyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

HRID 718599Notes

Reaction equation

HRID 718599 reaction equation
[CH:1]([C:3]1[N:4]=[C:5]2[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:9][CH:8]=[N:7][N:6]2[C:17]=1[C:18]1[CH:19]=[CH:20][C:21]([N:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)=[N:22][CH:23]=1)=O.[NH2:37][C:38]1[CH:47]=[CH:46][C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[N:39]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[O:14]1[CH2:15][CH2:16][N:11]([C:10]2[C:5]3[N:6]([C:17]([C:18]4[CH:19]=[CH:20][C:21]([N:24]5[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:31])[CH2:28][CH2:29]5)=[N:22][CH:23]=4)=[C:3]([CH2:1][NH:37][C:38]4[CH:47]=[CH:46][C:45]5[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=5)[N:39]=4)[N:4]=3)[N:7]=[CH:8][CH:9]=2)[CH2:12][CH2:13]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 113792-AminoquinolineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride3×HCID 117732472HCID 117732472, compound

Product 1

HCID 117732473tert-Butyl 4-(5-(8-morpholino-2-((quinolin-2-ylamino)methyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Crude compound 21b (140 mg, 0.284 mmol) was placed in a 50 mL round bottom flask equipped with a stir bar and then 2-aminoquinoline (49.1 mg, 0.340 mmol) was added. DCE (10 mL) and AcOH (32.5 μL, 0.567 mmol) were added and then NaBH(OAc)3 (180 mg, 0.851 mmol) was added as a solid. The reaction was stirred at rt for 20 h and then additional NaBH(OAc)3 (60.0 mg, 0.283 mmol) was added. After 24 h, more NaBH(OAc)3 (60.0 mg, 0.283 mmol) was added and the reaction was stirred for an additional 20 h. The reaction was poured into saturated NaHCO3 solution (30 mL) and extracted with DCM (3×10 mL), and then the combined organic extracts were dried over MgSO4 and filtered. The solvent was removed under reduced pressure. The crude product was chromatographed on a 12 g SiO2 pre-packed column eluting with 0-100% ACN/DCM to afford compound 21c. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.52 (d, J=2.0 Hz, 1H), 8.00 (d, J=5.4 Hz, 1H), 7.88 (dd, J=8.8, 2.2 Hz, 1H), 7.80 (d, J=9.0 Hz, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.58 (d, J=7.8 Hz, 1H), 7.52 (t, J=7.7 Hz, 1H), 7.21 (t, J=7.5 Hz, 1H), 6.76 (d, J=8.8 Hz, 1H), 6.71 (d, J=9.0 Hz, 1H), 6.08 (d, J=5.9 Hz, 1H), 5.49 (br. s., 1H), 4.87 (d, J=4.9 Hz, 2H), 3.88-4.01 (m, 8H), 3.52-3.65 (m, 8H), 1.50 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C34H39N9O3: 622.3 (M+H). Found: 622.3.

Workup

  1. customequipped with a stir bar
  2. waitAfter 24 h
  3. stirringthe reaction was stirred for an additional 20 h
  4. extractionextracted with DCM (3×10 mL)
  5. dry with materialthe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. customThe solvent was removed under reduced pressure
  8. customThe crude product was chromatographed on a 12 g SiO2 pre-packed column
  9. washeluting with 0-100% ACN/DCM

Sources & evidence

ORD record
ord-b2a669e499a2418399442b8555f83787
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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