Sodium Carbonate → HCID 73427039, compound

HRID 528463Notes

Reaction equation

HRID 528463 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[O:11][CH2:10][C:9]([CH3:13])([CH3:12])[O:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[N:30][C:31]([NH2:34])=[N:32][CH:33]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:12][C:9]1([CH3:13])[O:8][C:6]2[N:7]=[C:2]([C:28]3[CH:29]=[N:30][C:31]([NH2:34])=[N:32][CH:33]=3)[N:3]=[C:4]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:5]=2[O:11][CH2:10]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 867117472-Chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

Product 1

HCID 73427039HCID 73427039, compoundYield 71.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine (285 mg, 1.00 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (440 mg, 1.99 mmol), Pd(PPh3)2Cl2 (70 mg, 0.10 mmol) and sodium carbonate (3.3 mL, 3.3 mmol, 1M aqueous solution) in acetonitrile (7 mL) was degassed then heated at 120° C. for 30 minutes using microwave irradiation. The reaction mixture was diluted with methanol and DCM and absorbed onto diatomaceous earth. The resulting residue was purified by column chromatography (SiO2, gradient 0-4% methanol in DCM then SiO2, gradient 0-100% ethyl acetate in cyclohexane) affording 104 as a white solid (245 mg, 71%). LCMS: RT=3.28 min, [M+H]+=345. 1H NMR (400 MHz, DMSO): δ 8.90 (2H, s), 7.00 (2H, s), 3.97 (2H, s), 3.70 (8H, s), 1.35 (6H, s).

Workup

  1. customwas degassed
  2. custommicrowave irradiation
  3. additionThe reaction mixture was diluted with methanol and DCM
  4. customabsorbed onto diatomaceous earth
  5. customThe resulting residue was purified by column chromatography (SiO2, gradient 0-4% methanol in DCM

Sources & evidence

ORD record
ord-1e4ea04264ea493b9add2d2391620a5b
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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