Sodium Carbonate → N6-methyl-2-morpholino-N6-(tetrahydro-2H-pyran-4-yl)-4,5'-bipyrimidine-2',6-diamine

HRID 1043807Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][C:12]([NH2:15])=[N:13][CH:14]=2)O1.Cl[C:18]1[N:23]=[C:22]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:21]=[C:20]([N:30]([CH3:37])[CH:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:37][N:30]([CH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1)[C:20]1[N:21]=[C:22]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[N:23]=[C:18]([C:9]2[CH:14]=[N:13][C:12]([NH2:15])=[N:11][CH:10]=2)[CH:19]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To an argon flushed mixture of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (42 mg, 0.19 mmol), 6-chloro-N-methyl-2-morpholino-N-(tetrahydro-2H-pyran-4-yl)pyrimidin-4-amine (12 mg, 0.038 mmol) in THF (0.8 mL), and aq. Na2CO3 (2M, 0.27 mL) in a pressure vessel, was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (8 mg, 0.0095 mmol) in one portion. The pressure vessel was sealed and the mixture was heated in a microwave at 120° C. for 600 seconds. The crude mixture was filtered, concentrated under reduced pressure and purified by reverse phase preparative HPLC to give N6-methyl-2-morpholino-N6-(tetrahydro-2H-pyran-4-yl)-4,5′-bipyrimidine-2′,6-diamine (4.6 mg, 32%). LC/MS (m/z): 372.2 (MH+), Rt 1.76 minutes.

Workup

customTo an argon flushed
customThe pressure vessel was sealed
filtrationThe crude mixture was filtered
concentrationconcentrated under reduced pressure
custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record: ord-98672fae47a043bf8fd34a1c6af5644d
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08563549B2

Reaction notes

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