Sodium Bicarbonate → HCID 66558298, compound

HRID 1182972Notes

Reaction equation

HRID 1182972 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:12]=[N:13][CH:14]=2)O1.Cl[C:26]1[CH:27]=[CH:28][C:29]2[N:30]=[CH:31][N:32]=[C:33]([O:36][CH:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[C:34]=2[N:35]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.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].C(Cl)Cl>[O:40]1[CH2:39][CH2:38][CH:37]([O:36][C:33]2[C:34]3[N:35]=[C:26]([C:9]4[CH:10]=[C:11]([NH:15][C:16](=[O:23])[C:17]5[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=5)[CH:12]=[N:13][CH:14]=4)[CH:27]=[CH:28][C:29]=3[N:30]=[CH:31][N:32]=2)[CH2:42][CH2:41]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 68228547HCID 68228547, compound2×HCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 66558298HCID 66558298, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzamide (Intermediate 13) (0.07 g, 0.216 mmol), 6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 1) (0.063 g, 0.238 mmol), 1N aq. sodium bicarbonate (0.432 ml, 0.432 mmol) and PdCl2(dppf)-CH2Cl2 (0.018 g, 0.022 mmol) in dioxane (1.08 ml) was subjected to microwave irradiation for 1 hour at 110° C., and cooled to room temperature. The reaction mixture was filtered through a Celite pad and washed with DCM. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO2 (only EtOAc) to give N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzamide (0.058 g, 63%) as a pink solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.04-2.11 (2H, m), 2.23-2.27 (2H, m), 3.67-3.73 (2H, m), 4.10-4.15 (2H, m), 5.63-5.70 (1H, m), 7.53-7.56 (2H, m), 7.60-7.63 (1H, m), 7.94 (2H, d, J=7.2 Hz), 8.12 (1H, brs), 8.29 (1H, d, J=8.8 Hz), 8.36 (1H, d, J=8.8 Hz), 8.83 (1H, s), 8.91 (1H, d, J=2.8 Hz), 9.01 (1H, t, J=2.2 Hz), 9.20 (1H, d, J=2.0 Hz). m/z=428.2 [M+1]+.

Workup

  1. customirradiation for 1 hour at 110° C.
  2. filtrationThe reaction mixture was filtered through a Celite pad
  3. washwashed with DCM
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by column chromatography on SiO2 (only EtOAc)

Sources & evidence

ORD record
ord-01013b1ebe4c4c95940acdf25c3b1e75
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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