Acetic Acid → HCID 66712753, compound

HRID 1262298Notes

Reaction equation

HRID 1262298 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]3[N:20]=[CH:19][C:18]4=[CH:21][CH:22]=[C:23]([C:24]5[CH:25]=[C:26]([CH:30]=O)[CH:27]=[N:28][CH:29]=5)[N:17]4[N:16]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[CH3:32][S:33]([CH2:36][CH2:37][NH2:38])(=[O:35])=[O:34].Cl.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:32][S:33]([CH2:36][CH2:37][NH:38][CH2:30][C:26]1[CH:25]=[C:24]([C:23]2[N:17]3[C:18]([CH:19]=[N:20][C:15]([NH:14][C:11]4[CH:10]=[CH:9][C:8]([N:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[CH:13][CH:12]=4)=[N:16]3)=[CH:21][CH:22]=2)[CH:29]=[N:28][CH:27]=1)(=[O:35])=[O:34]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 43405612-(Methylsulfonyl)ethanamineHCID 5049666Sodium triacetoxyborohydrideHCID 86661695HCID 86661695, compound

Product 1

HCID 66712753HCID 66712753, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

Into a 8-dram vial, 5-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-pyridine-3-carbaldehyde (100.2 mg, 0.2424 mmol), 2-Methanesulfonyl-ethylamine; hydrochloride (0.2322 g, 1.454 mmol), 1,2-Dichloroethane (15.0 mL), and Acetic acid (100.0 uL, 1.759 mmol) were added and heated at 45° C. overnight. Sodium triacetoxyborohydride (0.1541 g, 0.7273 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours. The reaction was partitioned with saturated NaHCO3 and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum. The reaction mixture was purified via ISCO column chromatography with DCM and methanol as eluant (5 to 25% methanol). The collected fractions afforded (7-{5-[(2-Methanesulfonyl-ethylamino)-methyl]-pyridin-3-yl}-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine as a yellow solid (8 mg, 6%). LCMS (E/I+) 521.19 (M+H). NMR 1H (DMSO-d6)-9.27 (s, 1H), 9.19 (d, 1H, J=2.25 Hz), 8.97 (s, 1H), 8.57 (t, 1H, J=1.90 Hz), 8.52 (d, 1H, J=1.61 Hz), 7.56 (d, 2H, J=8.79 Hz), 7.27 (d, 1H, J=5.28 Hz), 6.95 (d, 1H, J=5.28 Hz), 6.92 (d, 1H, J=8.79 Hz), 3.84 (d, 2H, J=5.80 Hz), 3.25 (t, 2H, J=6.63 Hz), 3.08 (t, 4H, J=4.97 Hz), 3.00 (s, 3H), 2.94 (q, 2H, J=6.63 Hz), 2.46 (t, 4H, J=4.97 Hz), 2.24 (s, 3H).

Workup

  1. customThe reaction was partitioned with saturated NaHCO3 and DCM
  2. customThe organic was separated
  3. washwashed with Brine
  4. dry with materialdried over Na2SO4
  5. filtrationThe solid was filtered
  6. washwashed with DCM
  7. customThe solvent was removed under vacuum
  8. customThe reaction mixture was purified via ISCO column chromatography with DCM and methanol as eluant (5 to 25% methanol)

Sources & evidence

ORD record
ord-2a3835656b73447aa3a9b88ed96a337d
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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