N,N-Dimethylglycine → 1-[4-[4-(6-Amino-5-oxazolo[4,5-b]pyridin-2-yl-3-pyridyl)pyrazol-1-yl]-1-piperidyl]-2-dimethylamino-ethanone

HRID 908465Notes

Reaction equation

HRID 908465 reaction equation
F[B-](F)(F)F.N1([O+]=C(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[O:23]1[C:31]2[C:26](=[N:27][CH:28]=[CH:29][CH:30]=2)[N:25]=[C:24]1[C:32]1[C:33]([NH2:49])=[N:34][CH:35]=[C:36]([C:38]2[CH:39]=[N:40][N:41]([CH:43]3[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]3)[CH:42]=2)[CH:37]=1.[CH3:50][N:51]([CH3:56])[CH2:52][C:53](O)=[O:54].CN1CCOCC1>CN1C(=O)CCC1>[NH2:49][C:33]1[N:34]=[CH:35][C:36]([C:38]2[CH:39]=[N:40][N:41]([CH:43]3[CH2:44][CH2:45][N:46]([C:53](=[O:54])[CH2:52][N:51]([CH3:56])[CH3:50])[CH2:47][CH2:48]3)[CH:42]=2)=[CH:37][C:32]=1[C:24]1[O:23][C:31]2[C:26]([N:25]=1)=[N:27][CH:28]=[CH:29][CH:30]=2

Participants

6

Reactant 4

HCID 673N,N-DimethylglycineHCID 79724-MethylmorpholineHCID 576870643-Oxazolo[4,5-b]pyridin-2-yl-5-[1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amineHCID 178484680HCID 178484680, compound

Product 1

HCID 576871141-[4-[4-(6-Amino-5-oxazolo[4,5-b]pyridin-2-yl-3-pyridyl)pyrazol-1-yl]-1-piperidyl]-2-dimethylamino-ethanoneYield 45%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
25 °C

Procedure

Benzotriazol-1-yl-[bis(dimethylamino)methylene]oxonium tetrafluoroborate (96 mg) was added to a stirred suspension of 3-oxazolo[4,5-b]pyridin-2-yl-5-[1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (90 mg), 2-dimethylaminoacetic acid (27.0 mg) and 4-methylmorpholine (0.055 ml) in NMP (1 ml) at 25° C. The resulting solution was stirred at 25° C. for 2 hours. The reaction mixture was purified by preparative HPLC using a Waters OBD reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness, the solid was taken up in dichloromethane, dried over Magnesium sulphate, filtered and concentrated. A precipitate appeared which was diluted with diethyl ether, the solid was collected by filtration, washed with petroleum ether then triturated several hours with acetonitrile, filtered and dried under vacuum at 50° C. overnight to afford 1-[4-[4-(6-amino-5-oxazolo[4,5-b]pyridin-2-yl-3-pyridyl)pyrazol-1-yl]-1-piperidyl]-2-dimethylamino-ethanone (50.0 mg) as a solid. NMR Spectrum: (DMSOd6) 1.74-1.85 (m, 1H), 1.86-1.97 (m, 1H), 2.05-2.15 (m, 2H), 2.21 (s, 6H), 2.72-2.83 (m, 1H), 3.01-3.10 (m, 1H), 3.12-3.23 (m, 2H), 4.14-4.25 (m, 1H), 4.39-4.52 (m, 2H), 7.48 (dd, 1H), 7.68 (bs, 2H), 7.95 (s, 1H), 8.23 (dd, 1H), 8.36 (s, 1H), 8.47 (d, 1H), 8.56 (dd, 1H), 8.59 (d, 1H); Mass spectrum: M+H+ 447;

Workup

  1. customThe reaction mixture was purified by preparative HPLC
  2. additionThe fractions containing the desired compound
  3. customwere evaporated to dryness
  4. dry with materialdried over Magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionwas diluted with diethyl ether
  8. filtrationthe solid was collected by filtration
  9. washwashed with petroleum ether
  10. customthen triturated several hours with acetonitrile
  11. filtrationfiltered
  12. customdried under vacuum at 50° C. overnight

Sources & evidence

ORD record
ord-4ddf1179fc234ce1a1782f39ac67d7f3
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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