Ammonia → HCID 59453013, compound

HRID 419609Notes

Reaction equation

HRID 419609 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[CH:19][C:20]([O:34][CH2:35][CH3:36])=[C:21]([CH:33]=2)[C:22]([NH:24][C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=2[F:32])=[O:23])[CH:5]=[CH:4][N:3]=1.[CH2:37]([C:39]1[C:40]([N:49]2[CH2:54][CH2:53][N:52]([CH2:55][CH2:56][S:57]([CH3:60])(=[O:59])=[O:58])[CH2:51][CH2:50]2)=[CH:41][C:42]([O:46][CH2:47][CH3:48])=[C:43]([NH2:45])[CH:44]=1)[CH3:38].C1(C)C=CC(S(O)(=O)=O)=CC=1.N>C(O)C(F)(F)F.CO>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][C:22](=[O:23])[C:21]1[CH:33]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:45][C:43]3[CH:44]=[C:39]([CH2:37][CH3:38])[C:40]([N:49]4[CH2:54][CH2:53][N:52]([CH2:55][CH2:56][S:57]([CH3:60])(=[O:59])=[O:58])[CH2:51][CH2:50]4)=[CH:41][C:42]=3[O:46][CH2:47][CH3:48])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH2:35][CH3:36]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 59452866HCID 59452866, compoundHCID 594529415-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide

Product 1

HCID 59453013HCID 59453013, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
85 °C

Procedure

To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (0.43 g, 0.84 mmol) and (5-ethyl-2-(ethyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}phenyl)amine (0.30 g, 0.84 mmol) in trifluoroethanol (5 mL) was added p-toluene sulfonic acid (0.32 g, 1.7 mmol), and the vial was sealed and heated to 85° C. overnight. The reaction was then cooled to rt and excess NH3 in MeOH (10% in DCM) was added. The solution was transferred to a roundbottom flask and silica was added. The solvent was removed on a rotovap and the product purified on a 40 g ISCO column. Desired fractions were combined and rotovaped down. The resulting foam was dissolved in DCM and ether was added to provide the title compound (0.23 g, 0.26 mmol, 30% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.71 (s, 1H), 9.29 (d, J=6.2 Hz, 1H), 8.36 (s, 1H), 8.24 (d, J=5.3 Hz, 1H), 8.03 (s, 1H), 7.73-7.70 (m, 1H), 7.67 (d, J=9.0 Hz, 1H), 7.56 (s, 1H), 7.42-7.31 (m, 2H), 7.23 (d, J=8.4 Hz, 1H), 7.16 (t, J=8.2 Hz, 2H), 6.90 (t, J=6.6 Hz, 1H), 6.78 (s, 1H), 6.57 (d, J=5.3 Hz, 1H), 4.23 (q, J=7.3 Hz, 2H), 4.04 (q, J=7.1 Hz, 2H), 3.31-3.26 (m, 2H), 3.03 (s, 3H), 2.84-2.78 (m, 2H), 2.74 (t, J=6.5 Hz, 2H), 2.63-2.46 (m, 6H), 1.40 (t, J=6.8 Hz, 3H), 1.22 (t, J=6.9 Hz, 3H), 1.05 (t, J=7.5 Hz, 3H). MS (ESI) m/z=824 [M+H]+.

Workup

  1. customthe vial was sealed
  2. temperatureThe reaction was then cooled to rt
  3. customThe solution was transferred to a roundbottom flask
  4. additionsilica was added
  5. customThe solvent was removed on a rotovap
  6. customthe product purified on a 40 g ISCO column
  7. dissolutionThe resulting foam was dissolved in DCM
  8. additionether was added

Sources & evidence

ORD record
ord-288a0587e60a4b2787a7499c0917177c
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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