Dimethylformamide → HCID 66711067, compound

HRID 1262154Notes

Reaction equation

HRID 1262154 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]([NH:14][C:15]3[N:20]=[CH:19][C:18]4=[CH:21][CH:22]=[C:23]([C:24]5[CH:25]=[N:26][NH:27][CH:28]=5)[N:17]4[N:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH2:4][CH2:3]1.C(N(CC)C(C)C)(C)C.CN(C)C=O.[CH3:43][S:44](Cl)(=[O:46])=[O:45]>>[CH3:43][S:44]([N:26]1[CH:25]=[C:24]([C:23]2[N:17]3[C:18]([CH:19]=[N:20][C:15]([NH:14][C:10]4[CH:11]=[CH:12][CH:13]=[C:8]([N:5]5[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]5)[CH:9]=4)=[N:16]3)=[CH:21][CH:22]=2)[CH:28]=[N:27]1)(=[O:46])=[O:45]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 136360290HCID 136360290, compound

Product 1

HCID 66711067HCID 66711067, compoundYield 24%

Procedure

To a solution of [3-(4-Methyl-piperazin-1-yl)-phenyl]-[7-(1H-pyrazol-4-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine (1.00E2 mg, 0.267 mmol) and N,N-Diisopropylethylamine (48.8 uL, 0.280 mmol) in N,N-Dimethylformamide (12.1 mL, 156 mmol) was added Methanesulfonyl chloride (21.7 uL, 0.280 mmol). The reaction was stirred at rt overnight. LCMS 453.0 (M+H), HPLC rt=2.180 min, 97% purity. The reaction mixture was concentrated to remove DMF, diluted with CH2Cl2, and washed with sat'd aqueous NaHCO3. The organic layer was dried over MgSO4, filtered, and concentrated. Product was isolated as a yellow solid (29 mg, 24%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.30 (s, 1H), 9.03 (s, 1H0, 8.97 (s, 1H), 8.71 (s, 1H), 7.39 (d, J=8.3 Hz, 1H), 7.29 (d, J=4.6 Hz, 1H0, 7.22 (dd, J=8.3 Hz, 8.3 Hz, 1H), 7.05 (bm, 1H), 6.95 (d, J=4.6 Hz, 1H), 6.63 (dd, J=8.4 Hz, 1.4 Hz, 1H0, 3.62 (s, 3H), 3.12-3.10 (m, 4H), 2.45-2.43 (m, 4H), 2.21 (s, 3H).

Workup

  1. customLCMS 453.0 (M+H), HPLC rt=2.180 min, 97% purity
  2. concentrationThe reaction mixture was concentrated
  3. customto remove DMF
  4. additiondiluted with CH2Cl2
  5. washwashed with sat'd aqueous NaHCO3
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e7036df1aa454f4ebe9af50d1ebd1b96
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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