Sodium Carbonate → 5-(6-Cyclopropyl-4-morpholino-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)pyrimidin-2-amine

HRID 528476Notes

Reaction equation

HRID 528476 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[O:11][CH:10]([CH:12]3[CH2:14][CH2:13]3)[CH2:9][O:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[N:31][C:32]([NH2:35])=[N:33][CH:34]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>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.C(#N)C>[CH:12]1([CH:10]2[CH2:9][O:8][C:6]3[N:7]=[C:2]([C:29]4[CH:30]=[N:31][C:32]([NH2:35])=[N:33][CH:34]=4)[N:3]=[C:4]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:5]=3[O:11]2)[CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 867117582-Chloro-6-cyclopropyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

Product 1

HCID 734271365-(6-Cyclopropyl-4-morpholino-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)pyrimidin-2-amineYield 9.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with 2-chloro-6-cyclopropyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine (191 mg, 0.64 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (283 mg, 1.28 mmol), Pd(PPh3)2Cl2 (45 mg, 0.06 mmol), sodium carbonate (2.11 mL, 2.11 mmol, 1M aqueous solution) and acetonitrile (2.5 mL). The vessel was sealed then evacuated and refilled with argon (×3) before being heated at 120° C. for 30 minutes using microwave irradiation. The reaction mixture was filtered before being purified by column chromatography (SiO2, gradient 0-4% methanol in DCM). The resultant residue was triturated with diethyl ether to give 107 as a white solid (21 mg, 9%). LCMS: RT=3.54 min, [M+H]+=357. 1H NMR (400 MHz, DMSO-d6): δ 8.89 (2H, s), 7.00 (2H, s), 4.53 (1H, dd, J=11.48, 2.34 Hz), 4.22 (1H, dd, J=11.50, 7.87 Hz), 3.75-3.67 (8H, m), 3.65-3.58 (1H, m), 1.01-0.99 (1H, m), 0.63-0.55 (2H, m), 0.51-0.42 (2H, m).

Workup

  1. customThe vessel was sealed
  2. customthen evacuated
  3. additionrefilled with argon (×3)
  4. custommicrowave irradiation
  5. filtrationThe reaction mixture was filtered
  6. custombefore being purified by column chromatography (SiO2, gradient 0-4% methanol in DCM)
  7. customThe resultant residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-e6f12dc592644e448edb2b427ea56ac5
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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