N,N-Dimethylglycine → HCID 66712231, compound

HRID 1262139Notes

Reaction equation

HRID 1262139 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[N:17]3[C:12]([CH:13]=[N:14][C:15]([NH:18][C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([NH2:25])[CH:20]=4)=[N:16]3)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[CH3:26][N:27]([CH3:32])[CH2:28][C:29](O)=[O:30].CN(C)C=O.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C([O-])(O)=O.[Na+]>>[CH3:26][N:27]([CH3:32])[CH2:28][C:29]([NH:25][C:21]1[CH:22]=[CH:23][CH:24]=[C:19]([NH:18][C:15]2[N:14]=[CH:13][C:12]3=[CH:11][CH:10]=[C:9]([C:6]4[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[N:17]3[N:16]=2)[CH:20]=1)=[O:30]

Participants

8

Reactant 7

HCID 673N,N-DimethylglycineHCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 66712134HCID 66712134, compound

Product 1

HCID 66712231HCID 66712231, compound

Procedure

N-[7-(6-Methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-benzene-1,3-diamine (50.0 mg, 0.150 mmol; N,N-Dimethylglycine (18.6 mg, 0.180 mmol) N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (34.6 mg, 0.180 mmol; and N,N-Dimethylformamide (0.999 mL, 12.9 mmol) were combined in a vial and stirred at rt for 1 hour. LCMS showed partial conversion to product. Stirred an additional 2 hours. Added 5 extra eq of acid, DIEA, HOBT, and EDCI and stirred for 18 h. Reaction went to completion. Diluted reaction mixture with sat'd NaHCO3 and filtered off resulting ppt. Ppt was purified by ISCO silica gel chromatography (0-100% EtOAc in hexanes). Conc down to recover title compound as a yellow solid (11 mg, 13%). LCMS=418.0 (M+H), HPLC purity=93%, rt=2.218 min. 1H NMR (400 MHz, CDCl3, δ, ppm): 9.03 (s, 1H), 8.72 (s, 2H), 8.52 (dd, J=2.4 Hz, 8.7 Hz, 1H), 7.85 (s, 1H), 7.42 (d, J=7.3 Hz, 1H), 7.32-7.28 (m, 2H), 6.95 (d, J=4.6 Hz, 1H), 6.90-6.87 (m, 2H), 6.85 (d, J=4.5 Hz, 1H), 4.00 (s, 3H), 3.09 (s, 2H), 2.37 (s, 6H).

Workup

  1. stirringStirred an additional 2 hours
  2. stirringstirred for 18 h
  3. customReaction
  4. additionDiluted
  5. filtrationfiltered off
  6. customresulting ppt
  7. customPpt was purified by ISCO silica gel chromatography (0-100% EtOAc in hexanes)
  8. customConc down to recover title compound as a yellow solid (11 mg, 13%)
  9. customLCMS=418.0 (M+H), HPLC purity=93%, rt=2.218 min

Sources & evidence

ORD record
ord-ed2bff658aa74b51b848d83b6a749a2c
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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