Cesium carbonate → HCID 178476881, compound

HRID 1948119

Reaction equation

HRID 1948119 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([C@H:20]3[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]3)=[C:13]3[C:17]=2[C:16](=[O:18])[N:15]([CH3:19])[CH2:14]3)[C:5]([C:27]([F:30])([F:29])[F:28])=[CH:4][N:3]=1.[CH2:31]([O:33][P:34]([CH2:39][C:40]1[CH:41]=[N:42][C:43]([NH2:48])=[C:44]([O:46][CH3:47])[CH:45]=1)(=[O:38])[O:35][CH2:36][CH3:37])[CH3:32].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:31]([O:33][P:34]([CH2:39][C:40]1[CH:41]=[N:42][C:43]([NH:48][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:10]=[CH:11][C:12]([C@H:20]4[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]4)=[C:13]4[C:17]=3[C:16](=[O:18])[N:15]([CH3:19])[CH2:14]4)[C:5]([C:27]([F:30])([F:29])[F:28])=[CH:4][N:3]=2)=[C:44]([O:46][CH3:47])[CH:45]=1)(=[O:38])[O:35][CH2:36][CH3:37])[CH3:32]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86654065Diethyl[(6-amino-5-methoxypyridin-3-yl)methyl]phosphonate2×HCID 178479962HCID 178479962, compound2×

Product 1

HCID 178476881HCID 178476881, compoundYield 1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 7-{[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}-4-(trans-4-hydroxycyclohexyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 308C, 130.0 mg, 0.29 mmol), diethyl[(6-amino-5-methoxypyridin-3-yl)methyl]phosphonate (Compound 308A, 80.9 mg, 0.29 mmol), Pd(OAc)2 (3.31 mg, 0.015 mmol), Xantphos (17.1 mg, 0.029 mmol), and Cs2CO3 (192.2 mg, 0.59 mmol) in dry dioxane (1.2 mL) was bubbled nitrogen for 2 min. This mixture was then irradiated at 160° C. for 40 min in a CEM microwave reactor. After cooled to room temperature, the reaction mixture was filtered and the filtrate was concentrated and purified by silica gel chromatography (1-5% MeOH in DCM) to give 1.9 mg of the title compound (yield: 1%). 1H NMR (CDCl3, 400 MHz): δ=1.29 (t, J=7.2 Hz, 6H), 1.45 (m, 2H), 1.63 (m, 2H), 1.90 (m, 2H), 2.16 (m, 2H), 2.50 (m, 1H), 3.18 (d, J=21.2 Hz, 2H), 3.22 (s, 3H), 3.77 (m, 1H), 3.94 (s, 3H), 4.04-4.10 (m, 4H), 4.39 (s, 2H), 7.41 (d, J=8.4 Hz, 1H), 8.04 (s, 1H), 8.45 (s, 1H), 9.33 (d, J=8.0 Hz, 1H), 10.86 (s, 1H). MS (ES+): m/z 679.23 [MH+]. HPLC: tR=1.21 min (UPLC TOF, polar—3 min).

Workup

  1. customwas bubbled nitrogen for 2 min
  2. customThis mixture was then irradiated at 160° C. for 40 min in a CEM microwave reactor
  3. filtrationthe reaction mixture was filtered
  4. concentrationthe filtrate was concentrated
  5. custompurified by silica gel chromatography (1-5% MeOH in DCM)

Sources & evidence

ORD record
ord-52090e8b690d4ed9b8d2849627a77d98
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Linked notes

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