Ammonium Acetate → [3-(1-Amino-indan-5-yl)-imidazo[1,2-b]pyridazin-6-yl]-butyl-amine

HRID 870677Notes

Reaction equation

HRID 870677 reaction equation
[CH2:1]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[C:20](=O)[CH2:19][CH2:18]4)=[CH:13][N:14]=2)[N:11]=1)[CH2:2][CH2:3][CH3:4].C([O-])(=O)C.[NH4+].C([BH3-])#[N:31].[Na+]>CO>[NH2:31][CH:20]1[C:21]2[C:17](=[CH:16][C:15]([C:12]3[N:10]4[N:11]=[C:6]([NH:5][CH2:1][CH2:2][CH2:3][CH3:4])[CH:7]=[CH:8][C:9]4=[N:14][CH:13]=3)=[CH:23][CH:22]=2)[CH2:18][CH2:19]1

Participants

5

Reactant 3

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 866963775-(6-Butylamino-imidazo[1,2-b]pyridazin-3-yl)-indan-1-one

Product 1

HCID 86696378[3-(1-Amino-indan-5-yl)-imidazo[1,2-b]pyridazin-6-yl]-butyl-amineYield 52%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 5-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-indan-1-one (50 mg, 0.16 mmol), ammonium acetate (500 mg), and methanol (5 mL) was maintained at RT for 5 min, then treated with sodium cyanoborohydride (500 mg). The resulting mixture was heated to 50° C. and maintained 16 h, then cooled to RT and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were washed with brine, then dried (MgSO4), filtered and concentrated to afford a residue that was purified by reverse phase HPLC to afford [3-(1-amino-indan-5-yl)-imidazo[1,2-b]pyridazin-6-yl]-butyl-amine (26 mg, 52%) as a white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.22 (s, 1H), 8.12 (d, J=8.1 Hz, 1H), 7.78 (s, 1H), 7.54-7.66 (m, 2H), 6.72 (d, J=9.6 Hz, 1H), 4.77-4.83 (m, 1H), 3.38 (t, J=7.2 Hz, 2H), 3.18-3.30 (m, 1H), 3.01-3.13 (m, 1H), 2.59-2.73 (m, 1H), 2.06-2.22 (m, 1H), 1.72 (quin, J=7.4 Hz, 2H), 1.43-1.57 (m, 2H), 1.02 (t, J=7.3 Hz, 3H); LCMS (ESI) m/e 322.3 [(M+H)+, calcd for C19H24N5 322.2].

Workup

  1. temperatureThe resulting mixture was heated to 50° C.
  2. temperaturemaintained 16 h
  3. temperaturecooled to RT
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (2×)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford a residue that
  13. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-0c8ad3dd5fc3452682f8b82dfb90d692
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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