Cesium carbonate → HCID 49832276, compound

HRID 1945789Notes

Reaction equation

HRID 1945789 reaction equation
[NH2:1][CH:2]([OH:29])[C:3]([N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[S:14][C:15]3[N:16]=[C:17](Cl)[N:18]=[C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[C:20]=3[N:21]=2)[CH2:8][CH2:7]1)([CH3:5])[CH3:4].[CH3:30][C:31]1[O:32][C:33]2[CH:48]=[CH:47][CH:46]=[CH:45][C:34]=2[C:35]=1B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:4][C:3]([N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[S:14][C:15]3[N:16]=[C:17]([C:35]4[C:34]5[CH:45]=[CH:46][CH:47]=[CH:48][C:33]=5[O:32][C:31]=4[CH3:30])[N:18]=[C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[C:20]=3[N:21]=2)[CH2:8][CH2:7]1)([CH3:5])[C:2]([NH2:1])=[O:29]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 673417654,4,5,5-Tetramethyl-2-(2-methylbenzofuran-3-yl)-1,3,2-dioxaborolaneHCID 86648245HCID 86648245, compound

Product 1

HCID 49832276HCID 49832276, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 1-amino-2-[4-(5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl)piperazin-1-yl]-2-methylpropan-1-ol (100 mg, 0.23 mmol), 2-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzofuran (88 mg, 0.34 mmol), tetrakis(triphenylphosphine) palladium (26 mg, 0.02 mmol) and Cs2CO3 (148 mg, 0.45 mmol) in dioxane (6 mL) and H2O (3 mL) was purged with argon then heated at 140° C. for 30 min in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with DCM/MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 50-100%) to afford 211 as a cream solid (75 mg, 61%). LCMS (Method G): RT 10.35 min, [M+H]+ 536.4. 1H NMR (CDCl3, 400 MHz): δ 8.40-8.37 (m, 1 H); 7.46-7.42 (m, 1 H); 7.32-7.23 (m, 2 H); 7.10 (d, J=5.3 Hz, 1 H); 5.22 (d, J=5.3 Hz, 1 H); 4.40 (m, 4 H); 3.93-3.87 (m, 6 H); 2.92 (s, 3 H); 2.69 (m, 4 H); 2.62 (m, 4 H) and 1.26 (s, 6 H)

Workup

  1. customwas purged with argon
  2. washwas washed with DCM/MeOH
  3. washthe product eluted with 2M NH3/MeOH
  4. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 50-100%)

Sources & evidence

ORD record
ord-b4d1e1b4c3b642309b0bfaabafd2595a
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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