Sodium Bicarbonate → N-(5-(4-(1-methylpiperidin-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide

HRID 1182963Notes

Reaction equation

HRID 1182963 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([O:12][CH:13]3[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]3)[C:10]=2[N:11]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[C:30]([NH:34][S:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)(=[O:37])=[O:36])[CH:31]=[N:32][CH:33]=2)O1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[CH3:19][N:16]1[CH2:17][CH2:18][CH:13]([O:12][C:9]2[C:10]3[N:11]=[C:2]([C:28]4[CH:29]=[C:30]([NH:34][S:35]([C:38]5[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=5)(=[O:36])=[O:37])[CH:31]=[N:32][CH:33]=4)[CH:3]=[CH:4][C:5]=3[N:6]=[CH:7][N:8]=2)[CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 52936632N-[5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]benzenesulfonamide2×HCID 866710666-chloro-4-[(1-methyl-4-piperidinyl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 66558110N-(5-(4-(1-methylpiperidin-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamideYield 14.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloro-4-(1-methylpiperidin-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 6) (0.074 g, 0.265 mmol), N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzene sulfonamide (Intermediate 2) (0.143 g, 0.398 mmol), PdCl2(dppf)-CH2Cl2Adduct (43.4 mg, 53.0 μmol) and 1N aq. sodium bicarbonate (0.531 ml, 0.531 mmol) in dioxane (1.06 ml) was refluxed for 3 hours. After cooling to room temperature, the reaction mixture was filtered through a Celite pad and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by prep TLC (EtOAc only) to give N-(5-(4-(1-methylpiperidin-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide (0.018 g, 14%) as a yellow solid. 1H-NMR (DMSO-d6, Varian 400 MHz) δ 1.88-1.99 (2H, m), 2.12-2.21 (2H, m), 2.26 (3H, s), 2.28-2.36 (2H, m), 2.77-2.85 (2H, m), 5.43 (1H, s), 6.54 (1H, brs), 7.47-7.60 (4H, m), 7.83-7.89 (2H, m), 8.31-8.39 (2H, m), 8.49 (1H, d, J=8.8 Hz), 8.84 (1H, s), 8.91 (1H, s). m/z=477.2 [M+1]+.

Workup

  1. temperaturewas refluxed for 3 hours
  2. filtrationthe reaction mixture was filtered through a Celite pad
  3. washwashed with CH2Cl2
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by prep TLC (EtOAc only)

Sources & evidence

ORD record
ord-e72bdc8f362b4af69c7ea311c5d3ca91
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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