N-(tert-butoxycarbonyl)glycine → 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

HRID 1625236Notes

Reaction equation

HRID 1625236 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9]C(O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C(N=C=NCCCN(C)C)C.O.[OH:26]N1C2C=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[CH:65]=[CH:64][C:61]([C:62]#[N:63])=[C:60]([NH:66][CH:67]3[CH2:72][CH2:71][NH:70][CH2:69][CH2:68]3)[CH:59]=2)[N:40]=1)([CH3:38])[CH3:37]>CN(C=O)C.O.C(OCC)(=O)C>[C:62]([C:61]1[CH:64]=[CH:65][C:58]([N:41]2[C:42]3=[N:43][CH:44]=[CH:45][C:46]([C:48]4[CH:49]=[N:50][C:51]5[C:56]([CH:57]=4)=[CH:55][CH:54]=[CH:53][CH:52]=5)=[C:47]3[C:39]([CH:36]([CH3:38])[CH3:37])=[N:40]2)=[CH:59][C:60]=1[NH:66][CH:67]1[CH2:68][CH2:69][N:70]([O:26][CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:71][CH2:72]1)#[N:63]

Participants

8

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 675014474-{3-Isopropyl-4-(quinolin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}-2-(piperidin-4-ylamino)benzonitrile

Product 1

HCID 67501379tert-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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 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 (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

Sources & evidence

ORD record
ord-08dbe123e7354ede9edf18cdbf9035ca
Source dataset
uspto-grants-2014_07
Patent number
US08779142B2

Reaction notes

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