Cesium carbonate → HCID 49832276, compound

HRID 1922970Notes

Reaction equation

HRID 1922970 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.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=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 178418397HCID 178418397, compoundCatalystHCID 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-717528263cb74244b0c1ad090979c631
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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