Cesium carbonate → HCID 86726462, compound

HRID 1487634Notes

Reaction equation

HRID 1487634 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:29][CH:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=2[N:7]=1.[NH2:36][C:37]1[CH:38]=[CH:39][C:40]([C:45]([NH:47][CH3:48])=[O:46])=[N:41][C:42]=1[O:43][CH3:44].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.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]>[CH3:44][O:43][C:42]1[N:41]=[C:40]([C:45]([NH:47][CH3:48])=[O:46])[CH:39]=[CH:38][C:37]=1[NH:36][C:2]1[N:3]=[C:4]([O:29][CH:30]2[CH2:31][CH2:32][O:33][CH2:34][CH2:35]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:27])([CH3:26])[CH3:28])[C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86726461HCID 86726461, compoundHCID 86726463HCID 86726463, compound

Product 1

HCID 86726462HCID 86726462, compoundYield 82%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

The solution of 6-(2-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole (1 equiv), 5-amino-6-methoxy-N-methylpicolinamide (1.05 equiv), xantphos (0.2 equiv), tris(dibenzylideneacetone)dipalladium(0) (0.1 equiv) in 1,4-dioxane (0.16 M) was added cesium carbonate (1.4 equiv). The reaction mixture was stirred at 150° C. for 2 h under microwave irradiation. The reaction was filtered, and concentrated. The crude was purified using silica gel chromatography (0-90% ethyl acetate (with 10% 1N ammonia in MeOH) in hexane) to give the title compound (82% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm −0.11 (s, 9H) 0.84-0.93 (m, 2H) 1.63-1.76 (m, 2H) 2.03-2.16 (m, 2H) 2.64 (s, 3H) 2.84 (d, J=4.69 Hz, 3H) 3.49-3.65 (m, 4H) 3.70-3.80 (m, 2H) 4.12 (s, 3H) 5.52-5.55 (m, 1H) 5.58 (s, 2H) 7.60 (s, 1H) 7.65 (d, J=1.17 Hz, 2H) 7.70 (d, J=8.20 Hz, 1H) 7.91-7.99 (m, 1H) 8.03 (s, 1H) 8.41 (q, J=4.69 Hz, 1H) 8.91 (d, J=7.81 Hz, 1H); MS (ESI) m/z 660.5 [M+1]+.

Workup

  1. filtrationThe reaction was filtered
  2. concentrationconcentrated
  3. customThe crude was purified

Sources & evidence

ORD record
ord-f57fbcb01ef84d119eb3e457c16c6d7e
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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