Dimethylformamide → HCID 67501608, compound

HRID 921550Notes

Reaction equation

HRID 921550 reaction equation
C(O[C:6]([NH:8][CH2:9][C:10](O)=O)=[O:7])(C)(C)C.Cl.C(N=C=[N:18][CH2:19][CH2:20][CH2:21]N(C)C)C.O.O[N:27]1[C:31]2C=CC=CC=2N=N1.[CH:36]([C:39]1[C:47]2[C:42](=[N:43][CH:44]=[CH:45][C:46]=2[C:48]2[CH:49]=[N:50][C:51]3[C:56]([CH:57]=2)=[CH:55][CH:54]=[CH:53][CH:52]=3)[N:41]([C:58]2[C:59](NC3CCNCC3)=[C:60]([CH:63]=[CH:64][CH:65]=2)C#N)[N:40]=1)([CH3:38])[CH3:37].C[N:74]([CH:76]=[O:77])C>O.C(OCC)(=O)C>[NH2:27][CH2:31][C:6]([N:8]1[CH2:9][CH2:10][CH:19]([NH:18][C:60]2[CH:59]=[C:58]([N:41]3[C:42]4=[N:43][CH:44]=[CH:45][C:46]([C:48]5[CH:49]=[N:50][C:51]6[C:56]([CH:57]=5)=[CH:55][CH:54]=[CH:53][CH:52]=6)=[C:47]4[C:39]([CH:36]([CH3:37])[CH3:38])=[N:40]3)[CH:65]=[CH:64][C:63]=2[C:76]([NH2:74])=[O:77])[CH2:20][CH2:21]1)=[O:7]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 131734929HCID 131734929, compound

Product 1

HCID 67501608HCID 67501608, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-(Tert-butoxycarbonyl)glycine (0.021 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.029 g), and 1-hydroxybenzotriazole monohydrate (0.016 g) were added to a solution of compound (77a) (0.050 g) in DMF (1.0 mL), followed by stirring under argon flow at room temperature for 15 hr. The reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with saturated saline. The organic layer after the washing was dried over anhydrous sodium sulfate, and then the solvent was distilled away to obtain tert-butyl 2-{(4-(2-cyano-5-(3-isopropyl-4-(quinolin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)phenylamino)piperidin-1-yl}-2-oxaethylcarbamate, which was used in the subsequent reaction without being purified. According to Example 1(7), tert-butyl 2-{(4-(2-carbamoyl-5-(3-isopropyl-4-(quinolin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)phenylamino)piperidin-1-yl}-2-oxaethylcarbamate was prepared using tert-butyl 2-{(4-(2-cyano-5-(3-isopropyl-4-(quinolin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)phenylamino)piperidin-1-yl}-2-oxaethylcarbamate instead of compound (1f) and was used in the subsequent reaction without being purified. Tert-butyl 2-{4-(2-carbamoyl-5-(3-isopropyl-4-(quinolin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)phenylamino)piperidin-1-yl}-2-oxaethylcarbamate was dissolved in trifluoroacetic acid, followed by stirring at room temperature for 1 hr. The reaction solution was distributed between chloroform and saturated sodium bicarbonate water. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate. After distillation of the solvent, the residue was purified by neutral silica gel column chromatography (chloroform/methanol) to obtain compound (79) (0.035 g, the third stage yield: 55%) as a white solid.

Workup

  1. washthe organic layer was washed with saturated saline
  2. dry with materialThe organic layer after the washing was dried over anhydrous sodium sulfate
  3. distillationthe solvent was distilled away
  4. customto obtain tert-butyl 2-{(4-(2-cyano-5-(3-isopropyl-4-(quinolin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)phenylamino)piperidin-1-yl}-2-oxaethylcarbamate, which
  5. customwas used in the subsequent reaction
  6. customwithout being purified
  7. customwas prepared
  8. customwas used in the subsequent reaction
  9. customwithout being purified
  10. dissolutionTert-butyl 2-{4-(2-carbamoyl-5-(3-isopropyl-4-(quinolin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)phenylamino)piperidin-1-yl}-2-oxaethylcarbamate was dissolved in trifluoroacetic acid
  11. stirringby stirring at room temperature for 1 hr
  12. washThe organic layer was washed with saturated saline
  13. dry with materialdried over anhydrous sodium sulfate
  14. distillationAfter distillation of the solvent
  15. customthe residue was purified by neutral silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-54905d94c34840a39dcc34500afad930
Source dataset
uspto-grants-2016_03
Patent number
US09273045B2

Reaction notes

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