Dimethylamine → 1-[3-(1-{[tert-Butyl(diphenyl)silyl]oxy}-2-methylpropan-2-yl)-1-{3-[2-(dimethylamino)ethoxy]phenyl}-1H-pyrazol-5-yl]-3-[(1S,4R)-4-({3-[(2S)-2-methylpiperidin-1-yl][1,2,4]triazolo[4,3-a]pyridin-6-yl}oxy)-1,2,3,4-tetrahydronaphthalen-1-yl]urea

HRID 1402442Notes

Reaction equation

HRID 1402442 reaction equation
CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N:15]2[C:19]([NH:20][C:21](=[O:50])[NH:22][C@@H:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[C@H:26]([O:33][C:34]4[CH:35]=[CH:36][C:37]5[N:38]([C:40]([N:43]6[CH2:48][CH2:47][CH2:46][CH2:45][C@@H:44]6[CH3:49])=[N:41][N:42]=5)[CH:39]=4)[CH2:25][CH2:24]3)=[CH:18][C:17]([C:51]([CH3:72])([CH3:71])[CH2:52][O:53][Si:54]([C:67]([CH3:70])([CH3:69])[CH3:68])([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)[C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)=[N:16]2)[CH:10]=1)(=O)=O.[CH3:73][NH:74][CH3:75]>C1COCC1>[Si:54]([O:53][CH2:52][C:51]([C:17]1[CH:18]=[C:19]([NH:20][C:21]([NH:22][C@@H:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C@H:26]([O:33][C:34]3[CH:35]=[CH:36][C:37]4[N:38]([C:40]([N:43]5[CH2:48][CH2:47][CH2:46][CH2:45][C@@H:44]5[CH3:49])=[N:41][N:42]=4)[CH:39]=3)[CH2:25][CH2:24]2)=[O:50])[N:15]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:7][CH2:6][N:74]([CH3:75])[CH3:73])[CH:10]=2)[N:16]=1)([CH3:71])[CH3:72])([C:67]([CH3:68])([CH3:69])[CH3:70])([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1

Participants

4

Reactant 2

HCID 674DimethylamineHCID 86687289HCID 86687289, compound

Product 1

HCID 866872911-[3-(1-{[tert-Butyl(diphenyl)silyl]oxy}-2-methylpropan-2-yl)-1-{3-[2-(dimethylamino)ethoxy]phenyl}-1H-pyrazol-5-yl]-3-[(1S,4R)-4-({3-[(2S)-2-methylpiperidin-1-yl][1,2,4]triazolo[4,3-a]pyridin-6-yl}oxy)-1,2,3,4-tetrahydronaphthalen-1-yl]ureaYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of Intermediate 153i (131 mg, 0.13 mmol) in THF (0.8 mL) was treated with a 2M solution of dimethylamine in THF (1.3 mL, 2.6 mmol) and the mixture was stirred at 60° C. for 18 h. The cooled solution was concentrated in vacuo, and the residue was partitioned between DCM and water. The phases were separated and the aqueous layer was extracted with DCM (×2). The combined organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo to a brown gum. The gum was purified by FCC, using 0-8% (2N NH3/MeOH) in DCM, to give the title compound as a white foam (93 mg, 75%). LCMS (Method 3): Rt 3.91 min, m/z 960.6 [MH+].

Workup

  1. concentrationThe cooled solution was concentrated in vacuo
  2. customthe residue was partitioned between DCM and water
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with DCM (×2)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo to a brown gum
  8. customThe gum was purified by FCC

Sources & evidence

ORD record
ord-1ec52fdd4be74801bf1edc2e55e84834
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

Loading…