1,4-Dioxane → HCID 72550938, compound

HRID 1057061Notes

Reaction equation

HRID 1057061 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[CH:10]=[C:9]([N:11]3[CH2:15][CH2:14][C:13]([F:17])([F:16])[CH2:12]3)[N:8]=[C:7]([NH:18][C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=3)[CH:6]=2)[CH2:2]1.O1[CH2:34][CH2:33][O:32][CH2:31]C1.C(N(C(C)C)C(C)C)C.O1CC(=O)C1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[F:16][C:13]1([F:17])[CH2:14][CH2:15][N:11]([C:9]2[N:8]=[C:7]([NH:18][C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:26])[F:27])[CH:22]=[CH:21][N:20]=3)[CH:6]=[C:5]([CH:3]3[CH2:2][N:1]([CH:34]4[CH2:31][O:32][CH2:33]4)[CH2:4]3)[CH:10]=2)[CH2:12]1

Participants

6

Reactant 5

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 90067629HCID 90067629, compound

Product 1

HCID 72550938HCID 72550938, compoundYield 3.3%

Conditions

Temperature
50 °C

Procedure

To a solution of 4-(azetidin-3-yl)-6-(3,3-difluoropyrrolidin-1-yl)-N-[4-(trifluoromethyl)-2-pyridyl]pyridin-2-amine (1-d, 200 mg, 0.5008 mmol) in 1,4-dioxane (3.0 mL, 35 mmol) and N-ethyldiisopropylamine (0.26 mL, 3.0 equiv., 1.502 mmol) was added 3-oxetanone (219 mg, 6.0 equiv., 3.005 mmol), and the reaction was stirred at 50° C. for 1.5 h. After the reaction was cooled down, sodium triacetoxyborohydride (447 mg, 4.0 equiv., 2.003 mmol) was added in portions. The reaction was stirred at 25° C. overnight. The crude was submitted for HPLC purification to yield 7.5 mg (3.3%) white powder. 1H NMR (400 MHz, DMSO-d6) δ (delta) 9.91 (s, 1H), 8.70 (s, 1H), 8.44 (d, J=5.4 Hz, 1H), 7.14 (d, J=5.3 Hz, 1H), 6.62 (s, 1H), 6.00 (s, 1H), 4.58 (t, J=6.7 Hz, 2H), 4.41 (t, J=5.9 Hz, 2H), 3.85 (t, J=13.2 Hz, 2H), 3.75 (p, J=6.2 Hz, 1H), 3.63 (q, J=6.4, 6.0 Hz, 4H), 3.54 (p, J=7.7, 7.1 Hz, 1H), 3.20 (t, J=6.6 Hz, 2H), 2.58 (td, J=14.5, 7.3 Hz, 2H). LCMS: m/z 456 (M+H).

Workup

  1. temperatureAfter the reaction was cooled down
  2. stirringThe reaction was stirred at 25° C. overnight
  3. customThe crude was submitted for HPLC purification

Sources & evidence

ORD record
ord-f7ee798117db4fc6b02dc0d20e90464c
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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