tert-butyl (3S)-3-aminopyrrolidine-1-carboxylate → 6-[(3S)-3-aminopyrrolidin-1-yl]-N-[4-(ethyloxy)phenyl]imidazo[1,2-b]pyridazin-8-amine

HRID 2239829Notes

Reaction equation

HRID 2239829 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH3:20])=[CH:14][CH:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.[NH2:21][C@H:22]1[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23]1>O>[NH2:21][C@H:22]1[CH2:26][CH2:25][N:24]([C:2]2[CH:3]=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH3:20])=[CH:14][CH:13]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=2)[CH2:23]1

Participants

4

Reactant 2

HCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 866117086-chloro-N-(4-ethoxyphenyl)imidazo[1,2-b]pyridazin-8-amine

Product 1

HCID 593044326-[(3S)-3-aminopyrrolidin-1-yl]-N-[4-(ethyloxy)phenyl]imidazo[1,2-b]pyridazin-8-amineYield 3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 6-chloro-N-(4-ethoxyphenyl)imidazo[1,2-b]pyridazin-8-amine (26 mg, 0.090 mmol), prepared as described in example 1, step (1c) was added (S)-3-amino-1-N-boc-pyrrolidine (180 mg, 0.96 mmol). The mixture was microwaved at 225° C. for one hour. The melt was then cooled, water was added followed by extraction with dichloromethane. The organic layer was then concentrated in vacuo and purified by preparative HPLC to give 0.9 mg (2%) of the title compound as a TFA salt, (Note that during the reaction the Boc cleaves and the 1-nitrogen of the pyrrolidine adds). 1H NMR (500 MHz, MeOH) δ ppm 7.99 (1H, s), 7.88 (1H, s), 7.31 (2H, d, J=7.7 Hz), 7.03 (2H, d, J=7.7 Hz), 6.18 (1H, s), 4.07 (2H, q, J=6.9 Hz), 4.0 (1H, m), 3.80 (1H, m), 3.55 (3H, m), 2.50 (1H, m), 2.15 (1H, m), 1.40 (3H, t, J=6.9 Hz). LC/MS, m/e 339 (M+1). HPLC Rt, 1.83 min. YMC ODSC18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

Workup

  1. customThe mixture was microwaved at 225° C. for one hour
  2. temperatureThe melt was then cooled
  3. extractionfollowed by extraction with dichloromethane
  4. concentrationThe organic layer was then concentrated in vacuo
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-36a72bb99d4849b786d971ddb03953e5
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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