Tetrahydrofuran → HCID 57401364, compound

HRID 1262224Notes

Reaction equation

HRID 1262224 reaction equation
C([SiH2][O:6][C:7](C)(C)[C:8]1[CH:9]=[C:10]([C:14]2[N:22]3[C:17]([CH:18]=[N:19][C:20]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([CH:30]5[CH2:35][CH2:34][N:33]([CH2:36][C:37]([NH2:39])=[O:38])[CH2:32][CH2:31]5)=[CH:26][CH:25]=4)=[N:21]3)=[CH:16][CH:15]=2)[CH:11]=[CH:12][CH:13]=1)(C)(C)C.O1CCCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>>[OH:6][CH2:7][C:8]1[CH:9]=[C:10]([C:14]2[N:22]3[C:17]([CH:18]=[N:19][C:20]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([CH:30]5[CH2:31][CH2:32][N:33]([CH2:36][C:37]([NH2:39])=[O:38])[CH2:34][CH2:35]5)=[CH:26][CH:25]=4)=[N:21]3)=[CH:16][CH:15]=2)[CH:11]=[CH:12][CH:13]=1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 2724141Tetrabutylammonium FluorideHCID 137329043HCID 137329043, compound

Product 1

HCID 57401364HCID 57401364, compoundYield 39%

Procedure

2-[4-(4-{7-[3-(tert-Butyl-dimethyl-silanyloxymethyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-phenyl)-piperidin-1-yl]-acetamide (100 mg, 0.175 mmol) was dissolved in tetrahydrofuran (10.0 mL, 123 mmol) and 1.00 M tetra-n-butylammonium fluoride in tetrahydrofuran (0.193 mL, 0.193 mmol) was added. The reaction was stirred at room temperature for 3 hours and was then concentrated under reduced pressure. The residue was taken up in DMSO (2 mL) and purified by prep-HPLC using a gradient of 0-55% AcN/water both containing 0.1% TFA as the eluting solvent. The product was then taken up in MeOH (30 mL) and MP-carbonate (1.2 g) and stirred for 2 hours. The reaction was then filtered and concentrated under reduced pressure to obtain the title compound as a yellow foam (31 mg, 39%). LCMS (m/e) 457 (M+H); 1H-NMR (d6-DMSO, 400 MHz) δ 9.42 (s, 1H), 8.97 (s, 1H), 8.18 (s, 1H), 7.98 (d, 1H, J=7.7 Hz), 7.71 (d, 2H, J=8.3 Hz), 7.54-7.46 (m, 1H), 7.38 (d, 1H, J=7.6 Hz), 7.28-7.08 (m, 5H), 6.95 (d, 1H, J=4.6 Hz), 5.31 (bs, 1H), 4.62 (s, 2H), 2.97-2.88 (m, 2H), 2.88 (s, 2H), 2.49-2.38 (m, 1H), 2.22-2.08 (m, 2H), 1.79-1.67 (m, 4H).

Workup

  1. concentrationwas then concentrated under reduced pressure
  2. custompurified
  3. stirringMP-carbonate (1.2 g) and stirred for 2 hours
  4. filtrationThe reaction was then filtered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-43d8a5fda94b4fb4b91c6551c18047f6
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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