Potassium Phosphate, Tribasic → 4-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N'-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842789Notes

Reaction equation

HRID 1842789 reaction equation
[CH3:1][N:2]1[CH2:7][CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH2:4][CH2:3]1.Br[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([NH:26][C:27]2[N:32]=[C:31]([C:33]3[CH:34]=[N:35][N:36]4[CH2:41][CH2:40][CH2:39][CH2:38][C:37]=34)[CH:30]=[CH:29][N:28]=2)=[CH:20][C:19]=1[NH2:42].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH3:25][O:24][C:22]1[CH:23]=[C:18]([C:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH:6]=2)[C:19]([NH2:42])=[CH:20][C:21]=1[NH:26][C:27]1[N:32]=[C:31]([C:33]2[CH:34]=[N:35][N:36]3[CH2:41][CH2:40][CH2:39][CH2:38][C:37]=23)[CH:30]=[CH:29][N:28]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 207733711-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 866773464-bromo-6-methoxy-N-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine2×

Product 1

HCID 866772954-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N'-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamineYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

1,1 Bis(di-tert-butylphosphino)ferrocene palladium dichloride (16.7 mg, 0.03 mmol) was added to a solution of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (139 mg, 0.62 mmol), 4-bromo-6-methoxy-N-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine (Intermediate 137, 215 mg, 0.52 mmol), and K3PO4 (220 mg, 1.04 mmol) in 1,4-dioxane (6 mL) and water (1.5 mL, degassed for 20 minutes prior to use). The mixture was then heated at 100° C. for 1 h and then concentrated in vacuo. The resulting residue was dissolved in EtOAc and this solution was washed three times with water, then with brine. The solution was then dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-10% methanolic ammonia in CH2Cl2 gave the title compound (160 mg, 72%) as a tan solid after trituration with diethyl ether; 1H NMR: 1.79-1.87 (2H, m), 1.96-2.03 (2H, m), 2.29 (3H, s), 2.34-2.40 (2H, m), 2.58 (2H, t), 2.98-3.02 (2H, m), 3.15 (2H, t), 3.75 (3H, s), 4.12 (2H, t), 4.32 (2H, br s), 5.67-5.71 (1H, m), 6.60 (1H, s), 7.01 (1H, d), 7.58 (1H, s), 7.69 (1H, s), 8.09 (1H, s), 8.32 (1H, d); m/z: ES+ MH+ 432.72.

Workup

  1. customdegassed for 20 minutes
  2. concentrationconcentrated in vacuo
  3. dissolutionThe resulting residue was dissolved in EtOAc
  4. washthis solution was washed three times with water
  5. dry with materialThe solution was then dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customPurification by FCC
  8. washeluting with 0-10% methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-4ddf9387176d46cdb420bdb1181f7a35
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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