2-(5-(Trimethylstannyl)pyridin-2-yl)propan-2-ol → 6-(6-(2-Hydroxypropan-2-yl)pyridin-3-yl)-4-(2-morpholinoethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

HRID 717138Notes

Reaction equation

HRID 717138 reaction equation
Br[C:2]1[N:3]=[C:4]2[N:11]([CH2:12][CH2:13][N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH2:10][C:9](=[O:20])[NH:8][C:5]2=[N:6][CH:7]=1.C[Sn](C)(C)[C:23]1[CH:24]=[CH:25][C:26]([C:29]([OH:32])([CH3:31])[CH3:30])=[N:27][CH:28]=1>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:32][C:29]([C:26]1[N:27]=[CH:28][C:23]([C:2]2[N:3]=[C:4]3[N:11]([CH2:12][CH2:13][N:14]4[CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)[CH2:10][C:9](=[O:20])[NH:8][C:5]3=[N:6][CH:7]=2)=[CH:24][CH:25]=1)([CH3:31])[CH3:30]

Participants

5

Reactant 2

HCID 666077842-(5-(Trimethylstannyl)pyridin-2-yl)propan-2-olHCID 866446456-Bromo-4-(2-morpholinoethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Product 1

HCID 582983226-(6-(2-Hydroxypropan-2-yl)pyridin-3-yl)-4-(2-morpholinoethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneYield 27%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

6-Bromo-4-(2-morpholinoethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (0.228 g, 0.666 mmol) and 2-(5-(trimethylstannyl)pyridin-2-yl)propan-2-ol (0.220 g, 0.733 mmol) were combined in dimethylformamide (3 mL). Solution was purged with nitrogen gas followed by the addition of dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane (0.109 g, 0.133 mmol). Solution was heated to 100° C. for 2 h. Solution was condensed under reduced pressure and the resulting oil purified via reverse-phase-preparative HPLC (5-60% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min) and desired fractions were loaded onto a Strata-XC ion exchange column. The column was washed successively with water, acetonitrile, methanol and 5% ammonium hydroxide in methanol. The product eluted with the 5% ammonium hydroxide in methanol and was concentrated under reduced pressure and dried to afford the title compound (0.070 g, 0.18 mmol, 26% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm) 11.33 (br. s., 1H), 9.05 (d, J=1.56 Hz, 1H), 8.27 (dd, J=8.59, 2.34 Hz, 1H), 8.06 (s, 1H), 7.72 (d, J=8.59 Hz, 1H), 5.27 (s, 1H), 4.29 (s, 2H), 3.71 (t, J=6.44 Hz, 2H), 3.54 (t, J=4.49 Hz, 4H), 2.62 (t, J=6.44 Hz, 2H), 2.40-2.48 (m, 4H), 1.46 (s, 6H); MS (ESI) m/z 399.2 [M+1]+; mp 239-241° C.

Workup

  1. customSolution was purged with nitrogen gas
  2. customcondensed under reduced pressure
  3. customthe resulting oil purified via reverse-phase-preparative HPLC (5-60% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  4. washThe column was washed successively with water, acetonitrile, methanol and 5% ammonium hydroxide in methanol
  5. washThe product eluted with the 5% ammonium hydroxide in methanol
  6. concentrationwas concentrated under reduced pressure
  7. customdried

Sources & evidence

ORD record
ord-e7749477784747bd8b755b08d89f407f
Source dataset
uspto-grants-2015_11
Patent number
US09193692B2

Reaction notes

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