Sodium Bicarbonate → HCID 66558476, compound

HRID 1485572Notes

Reaction equation

HRID 1485572 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:12][CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[C:10]=2[N:11]=1.[Cl:26][C:27]1[C:32]([NH:33][S:34]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=2[F:44])(=[O:36])=[O:35])=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][N:28]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[Cl:26][C:27]1[N:28]=[CH:29][C:30]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH:12][CH:13]4[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])[CH2:15][CH2:14]4)[C:10]=3[N:11]=2)=[CH:31][C:32]=1[NH:33][S:34]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=1[F:44])(=[O:36])=[O:35]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 86671079HCID 86671079, compound2×HCID 86671080N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide2×

Product 1

HCID 66558476HCID 66558476, compoundYield 4.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of tert-butyl 4-(6-chloropyrido[3,2-d]pyrimidin-4-ylamino)piperidine-1-carboxylate (Intermediate 24) (0.050 g, 0.137 mmol), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)pyridine-3-yl)-2,4-difluorobenzenesulfonamide (Intermediate 3) (0.065 g, 0.151 mmol), PdCl2(dppf)-CH2Cl2Adduct (5.61 mg, 6.87 μmol) and 1 N aq. sodium bicarbonate (0.275 ml, 0.275 mmol) in dioxane (1.40 ml) subjected to microwave irradiation for 1 hour at 110° C. After cooling to room temperature, the reaction mixture was filtered through Celite and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by prep TLC (Hex:EtOAc=1:2) to give tert-butyl 4-(6-(6-chloro-5-(2,4-difluorophenylsulfonamido)pyridin-3-yl)pyrido[3,2-d]pyrimidin-4-ylamino)piperidine-1-carboxylate (3.90 mg, 4.5%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.48 (9H, s), 1.55-1.72 (2H, m), 2.05-2.22 (2H, m), 2.92-3.12 (2H, m), 4.02-4.25 (2H, m), 4.30-4.48 (1H, m), 6.90-7.04 (2H, m), 7.14 (1H, J=8.0 Hz), 7.80-7.92 (1H, m), 8.07 (1H, d, J=8.8 Hz), 8.22 (1H, d, J=8.8 Hz), 8.69 (1H, s), 8.70 (1H, br s), 8.79 (1H, br s). m/z=632.2 [M+1]+.

Workup

  1. customirradiation for 1 hour at 110° C
  2. filtrationthe reaction mixture was filtered through Celite
  3. washwashed with CH2Cl2
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by prep TLC (Hex:EtOAc=1:2)

Sources & evidence

ORD record
ord-dfbfd079aa7342a98ccdf8b7688ee045
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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