Acetyl chloride → HCID 58529379, compound

HRID 1972895Notes

Reaction equation

HRID 1972895 reaction equation
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33](Cl)(=[O:35])[CH3:34].C(N(CC)C(C)C)(C)C>C1COCC1>[C:33]([N:30]1[CH2:31][CH2:32][CH:27]([C:19]2[N:20]3[C:25]([C:24]([NH2:26])=[N:23][CH:22]=[N:21]3)=[C:17]([C:12]3[CH:13]=[CH:14][C:15]4[C:10]([CH:11]=3)=[N:9][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:16]=4)[CH:18]=2)[CH2:28][CH2:29]1)(=[O:35])[CH3:34]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 16066662HCID 16066662, compound

Product 1

HCID 58529379HCID 58529379, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(2-benzyl-2H-indazol-6-yl)-7-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine (150 mg, 0.33 mmol) in THF (1.88 mL) was added acetyl chloride (26 μL, 0.36 mmol) and N,N-diisopropylethylamine (170 μL, 0.98 mmol). The reaction was stirred at rt for 17 h. The mixture was partitioned between EtOAc (25 mL) and H2O (25 mL). The layers were separated and the organic phase was washed with H2O (20 mL), brine, dried (Na2SO4) and concentrated. The crude material was purified by ISCO® chromatography using a gradient of 0 to 10% MeOH in EtOAc. The isolated compound was crystallized from EtOAc/hexanes to afford 64 mg (42%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1 H), 7.90 (s, 1 H), 7.79 (d, 1 H), 7.58 (s, 1 H), 7.28-7.38 (m, 5 H), 7.13 (dd, 1 H), 6.59 (s, 1 H), 5.64 (s, 2 H), 4.48 (d, 1 H) 3.89 (s, 1 H), 3.32-3.41 (m, 3 H), 3.19 (s, 1 H), 2.67 (d, 1 H), 1.98-2.07 (m, 3 H), 1.66 (d, 1 H), 1.51 (s, 1 H); ES-MS m/z 466.4 [M+H]+, HPLC RT (min) 2.49.

Workup

  1. customThe mixture was partitioned between EtOAc (25 mL) and H2O (25 mL)
  2. customThe layers were separated
  3. washthe organic phase was washed with H2O (20 mL), brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude material was purified by ISCO® chromatography
  7. customThe isolated compound was crystallized from EtOAc/hexanes

Sources & evidence

ORD record
ord-fda964e539ea4cd3b078f74f3fae0619
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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