Triethylamine → tert-Butyl N-[2-[[5-[(4-methoxyphenyl)methylcarbamoyl]-1,3-dimethyl-pyrazolo[3,4-b]pyridin-4-yl]amino]ethyl]carbamate

HRID 333090Notes

Reaction equation

HRID 333090 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][NH:11][C:12]1[C:17]([C:18](O)=[O:19])=[CH:16][N:15]=[C:14]2[N:21]([CH3:25])[N:22]=[C:23]([CH3:24])[C:13]=12)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C(N=C=NCCCN(C)C)C.ON1C2=NC=CC=C2N=N1.C(N(CC)CC)C.[CH3:55][O:56][C:57]1[CH:62]=[CH:61][C:60]([CH2:63][NH2:64])=[CH:59][CH:58]=1>CN(C)C=O>[CH3:55][O:56][C:57]1[CH:62]=[CH:61][C:60]([CH2:63][NH:64][C:18]([C:17]2[C:12]([NH:11][CH2:10][CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[C:13]3[C:23]([CH3:24])=[N:22][N:21]([CH3:25])[C:14]3=[N:15][CH:16]=2)=[O:19])=[CH:59][CH:58]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 754524-MethoxybenzylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866911744-[2-(tert-Butoxycarbonylamino)ethylamino]-1,3-dimethyl-pyrazolo[3,4-b]pyridine-5-carboxylic acid

Product 1

HCID 86691175tert-Butyl N-[2-[[5-[(4-methoxyphenyl)methylcarbamoyl]-1,3-dimethyl-pyrazolo[3,4-b]pyridin-4-yl]amino]ethyl]carbamateYield 279.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[2-(tert-butoxycarbonylamino)ethylamino]-1,3-dimethyl-pyrazolo[3,4-b]pyridine-5-carboxylic acid (96.1 mg, 0.275 mmol) in N,N-dimethylformamide (2.5 ml) was subsequently added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (91.8 mg, 0.479 mmol), 3-hydroxytriazolo[4,5-b]pyridine (39.7 mg, 0.292 mmol) and triethylamine (0.115 ml, 0.825 mmol). The reaction mixture was stirred for five minutes after which (4-methoxyphenyl)methanamine (0.072 ml, 0.550 mmol) was added. The reaction mixture was stirred at room temperature over night. The reaction mixture was partitioned between water (40 ml) and EtOAc (50 ml). The organic layer was separated and the aqueous phase was further extracted with EtOAc (3×40 ml) and dichloromethane (1×50 ml). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to yield 360 mg of a yellow liquid which was purified by column chromatography (silicagel using a gradient of MeOH (1-7%) in dichloromethane) to give 43 mg of a colorless sticky oil (0.092 mmol, 33%) MS (ESI) m/z=469.3 [M+1]+.

Workup

  1. additionwas added
  2. customThe reaction mixture was partitioned between water (40 ml) and EtOAc (50 ml)
  3. customThe organic layer was separated
  4. extractionthe aqueous phase was further extracted with EtOAc (3×40 ml) and dichloromethane (1×50 ml)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-798fcdbfd6d247bb8c2d9306fae3bf87
Source dataset
uspto-grants-2014_11
Patent number
US08877934B2

Reaction notes

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