1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Gsk-2256098

HRID 1472540Notes

Reaction equation

HRID 1472540 reaction equation
[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=2[C:21]([OH:23])=O)=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:16])[CH3:15])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.Cl.[CH3:50][O:51][NH2:52].C(N(C(C)C)CC)(C)C>CN(C)C=O.C(O)(=O)C.O>[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=2[C:21]([NH:52][O:51][CH3:50])=[O:23])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:15])[CH3:16])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 593144592-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)benzoic acid

Product 1

HCID 46214930Gsk-2256098Yield 94.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]benzoic acid (67 g, 174 mmol) and 1-hydroxybenzotriazole (29.3 g, 191 mmol) in N,N-dimethylformamide (700 mL) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (36.6 g, 191 mmol) and the solution was stirred for 30 minutes. O-Methylhydroxylamine hydrochloride (15.95 g, 191 mmol) was added and the solution stirred for additional 15 minutes, the cooled down to the 0° C. and diisopropylethlyamine (91 mL, 521 mmol) was added dropwise. The reaction mixture was stirred overnight at room temperature. Water (4000 mL) was added and the solution was acidified with acetic acid (20 mL). The solution was extracted 2×2 L of ethyl acetate. The organic was washed with water (1 L), brine, and dried over MgSO4, filtered and evaporated. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridiny)amino]-N-(methyloxy)benzamide (74 g, 164 mmol, 94% yield, 92% pure) was isolated as a yellow foam. 1H NMR (400 MHz, DMSO-d6) ppm 1.27 (d, J=6.57 Hz, 6 H) 2.10 (s, 3 H) 3.71 (s, 3 H) 4.39 (quin, J=6.51 Hz, 1 H) 5.93 (s, 1 H) 6.66 (s, 1 H) 7.08 - 7.19 (m, 1 H) 7.49 - 7.64 (m, 3 H) 7.98 (s, 1 H) 8.50 (s, 1 H) 9.50 (s, 1 H) 11.93 (s, 1 H).; HPLC Rt=2.13 min, MS (ESI): [M+H]+=415.1.

Workup

  1. stirringthe solution stirred for additional 15 minutes
  2. additionwas added dropwise
  3. stirringThe reaction mixture was stirred overnight at room temperature
  4. extractionThe solution was extracted 2×2 L of ethyl acetate
  5. washThe organic was washed with water (1 L), brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-c34a173449e74ce98dcbedb13288fbf6
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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