Potassium Carbonate → HCID 118116875, compound

HRID 1487346Notes

Reaction equation

HRID 1487346 reaction equation
[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])=[CH:7][C:6]=1[C:17]1[C:22]([O:23][CH2:24][CH3:25])=[CH:21][C:20](=[O:26])[N:19]([CH3:27])[CH:18]=1.[C:33]([O-:36])([O-])=O.[K+].[K+]>>[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]([CH2:2][C@H:3]2[CH2:33][O:36][CH2:6][CH2:5][O:4]2)[S:12]([CH2:15][CH3:16])(=[O:13])=[O:14])=[CH:7][C:6]=1[C:17]1[C:22]([O:23][CH2:24][CH3:25])=[CH:21][C:20](=[O:26])[N:19]([CH3:27])[CH:18]=1

Participants

3

Reactant 2

HCID 11430Potassium CarbonateHCID 90018193HCID 90018193, compound

Product 1

HCID 118116875HCID 118116875, compoundYield 75.5%

Procedure

A stock solution of Example 72A (0.16 M in DMF, 200 μL, 0.03 mmol Example 72A (1.0 equivalent)), K2CO3 (13.4 mg, 0.096 mmol, 3.2 equivalents) and (25)-4-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate (0.04 M in DMA, 89 μL, 0.036 mmol, 1.2 equivalents), were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 1.8 mL internal volume) set at 100° C., and passed through the reactor at 180 μL min−1 (10 minute residence time). Upon exiting the reactor, the reaction was loaded directly into an injection loop and purified by preparative HPLC on a Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (50 mm×21.2 mm). A gradient of acetonitrile (A) and 0.1% ammonium acetate in water (B) was used, at a flow rate of 30 mL/min (0-0.5 min 5% A, 0.5-6 5 min linear gradient 5-60% A, 6.5-7.0 min linear gradient 60-100% A, 7.0-8.9 min 100% A, 8.9-9.0 min linear gradient 100-5% A, 9.0-10 min 5% A) to yield the title compound (6.39 mg, 32% yield). 1H NMR (400 MHz, DMSO-d6/D2O) δ 7.56 (m, 1H), 7.44-7.38 (m, 2H), 7.29 (m, 1H), 7.15-7.03 (m, 2H), 6.96 (m, 1H), 5.87 (s, 1H), 4.02 (q, J=7.0 Hz, 2H), 3.80 (m, 1H),3.77-3.72 (m, 2H), 3.70-3.62 (m, 2H), 3.61-3.49 (m, 4H), 3.44 (s, 3H), 3.20 (m, 2H), 1.31 (t, J=7.4 Hz, 3H), 1.24 (t, J=7.0 Hz, 3H). MS (ESI+) m/z 565.1 (M+H)+.

Workup

  1. additionmixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter)
  2. customset at 100° C.
  3. custompassed through the reactor at 180 μL min−1 (10 minute residence time)
  4. custompurified by preparative HPLC on a Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (50 mm×21.2 mm)
  5. customwas used, at a flow rate of 30 mL/min (0-0.5 min 5% A, 0.5-6 5 min linear gradient 5-60% A, 6.5-7.0 min linear gradient 60-100% A, 7.0-8.9 min 100% A, 8.9-9.0 min linear gradient 100-5% A, 9.0-10 min 5% A)

Sources & evidence

ORD record
ord-2272c81d8af54c5c903b828e2a9fe859
Source dataset
uspto-grants-2016_08
Patent number
US09428514B2

Reaction notes

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