(E)-tert-Butyl 3-(3-(hex-1-enyl)imidazo[1,2-b]pyridazin-6-ylamino)propylcarbamate → (E)-N1-(3-(Hex-1-enyl)imidazo[1,2-b]pyridazin-6-yl)propane-1,3-diamine

HRID 1162145Notes

Reaction equation

HRID 1162145 reaction equation
[CH:1](/[C:7]1[N:11]2[N:12]=[C:13]([NH:16][CH2:17][CH2:18][CH2:19][NH:20]C(=O)OC(C)(C)C)[CH:14]=[CH:15][C:10]2=[N:9][CH:8]=1)=[CH:2]\[CH2:3][CH2:4][CH2:5][CH3:6]>C(O)(C(F)(F)F)=O>[CH:1](/[C:7]1[N:11]2[N:12]=[C:13]([NH:16][CH2:17][CH2:18][CH2:19][NH2:20])[CH:14]=[CH:15][C:10]2=[N:9][CH:8]=1)=[CH:2]\[CH2:3][CH2:4][CH2:5][CH3:6]

Participants

3

Reactant 1

HCID 86621015(E)-tert-Butyl 3-(3-(hex-1-enyl)imidazo[1,2-b]pyridazin-6-ylamino)propylcarbamate

Product 1

HCID 59519547(E)-N1-(3-(Hex-1-enyl)imidazo[1,2-b]pyridazin-6-yl)propane-1,3-diamineYield 29%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

The product from step B was stirred in TFA (3 mL) for 3 h. The reaction mixture was concentrated and partitioned between ethyl acetate and saturated sodium carbonate solution and the organic layer removed and concentrated. Purification by column chromatography (12 g ISCO column eluting with methylene chloride and methanol/ammonia mixture (10:1); gradient 100% methylene chloride to 70% methylene chloride over 30 min at 25 mL/min) provided the title compound (26 mg, 29%) as a yellow solid; 1H NMR (500 MHz, CD3OD) δ 7.56 (d, J=9.6 Hz, 1H), 7.45 (s, 1H), 6.69-6.61 (m, 3H), 3.51 (t, J=6.4 Hz, 2H), 3.07 (t, J=7.4 Hz, 2H), 2.29-2.27 (m, 2H), 2.06 (m, 2H), 1.50-1.43 (m, 4H), 0.96 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CD3OD) δ 155.3, 133.2, 128.8, 128.6, 125.7, 116.7, 113.6, 39.5, 39.0, 34.4, 32.9, 27.9, 23.4, 14.3 (one aromatic carbon overlapping); HPLC tR=10.9 min (Luna), 94.7%; ES-MS: (M+H)=274 m/z.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between ethyl acetate and saturated sodium carbonate solution
  3. customthe organic layer removed
  4. concentrationconcentrated
  5. customPurification
  6. washby column chromatography (12 g ISCO column eluting with methylene chloride and methanol/ammonia mixture (10:1); gradient 100% methylene chloride to 70% methylene chloride over 30 min at 25 mL/min)

Sources & evidence

ORD record
ord-ca078dcac7f04ec58889b539d5961ebe
Source dataset
uspto-grants-2010_10
Patent number
US07820670B2

Reaction notes

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