1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 9-(4,4-Dimethylcyclohexyl)-8-methoxy-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 79199Notes

Reaction equation

HRID 79199 reaction equation
Cl[C:2]1[C:3]([O:24][CH3:25])=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[C:9]([NH:15][CH:16]2[CH2:21][CH2:20][C:19]([CH3:23])([CH3:22])[CH2:18][CH2:17]2)=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH3:22][C:19]1([CH3:23])[CH2:20][CH2:21][CH:16]([N:15]2[C:9]3[N:10]=[C:11]([NH2:14])[N:12]=[CH:13][C:8]=3[C:7]3[CH:6]=[CH:5][N:4]=[C:3]([O:24][CH3:25])[C:2]2=3)[CH2:17][CH2:18]1

Participants

6

Reactant 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 583000415-(3-Chloro-2-methoxy-4-pyridinyl)-N4-(4,4-dimethylcyclohexyl)-2,4-pyrimidinediamine

Product 1

HCID 582997769-(4,4-Dimethylcyclohexyl)-8-methoxy-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineYield 133.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a 30 mL microwave reaction vessel were placed compound 332 (0.55 g, 1.5 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.14 g, 0.15 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.22 g, 0.38 mmol), and sodium tert-butoxide (0.37 g, 3.8 mmol) followed by 1,4-dioxane (15 mL). The vessel was purged with N2 for 5 min, then capped and subjected to microwave condition (3 h at 140° C.). After the volatiles were removed, the crude mixture was taken up in 4% methanol/DCM and subjected to combi-flash column chromatography (1% to 7% methanol in DCM) to give crude compound 333 as an off-white solid (0.65 g). 1H NMR (500 MHz, DMSO-d6) δ ppm 9.01 (1 H, s), 7.92 (1 H, d, J=5.1 Hz), 7.59 (1 H, d, J=4.9 Hz), 6.86 (2 H, br. s.), 4.98-5.14 (1 H, m), 4.06 (3 H, s), 1.53 (4 H, br. s.), 1.31-1.44 (2 H, m), 1.16 (3 H, s), 1.00 (3 H, s). LCMS-ESI (POS), M/Z, M+1: Found 326.1.

Workup

  1. customTo a 30 mL microwave reaction vessel were placed
  2. customThe vessel was purged with N2 for 5 min
  3. customcapped
  4. customsubjected to microwave condition (3 h at 140° C.)
  5. customAfter the volatiles were removed

Sources & evidence

ORD record
ord-68428ef3b51e4414a1bbb2df68237214
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

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