6-bromo-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one → HCID 71471734, compound

HRID 925625Notes

Reaction equation

HRID 925625 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]3[N:15]([CH3:16])[CH2:14][CH2:13][CH2:12][C:11]=13)[N:8]=[CH:7][N:6]([C@H:17]1[CH2:22][CH2:21][CH2:20][CH2:19][C@@H:18]1[OH:23])[C:5]2=[O:24].[Cl-].[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][Zn+])=[CH:29][N:28]=1>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:26][C:27]1[N:28]=[CH:29][C:30]([CH2:33][C:2]2[CH:3]=[C:4]3[C:9](=[C:10]4[N:15]([CH3:16])[CH2:14][CH2:13][CH2:12][C:11]=24)[N:8]=[CH:7][N:6]([C@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][C@@H:18]2[OH:23])[C:5]3=[O:24])=[CH:31][CH:32]=1

Participants

5

Reactant 2

HCID 710421236-bromo-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-oneHCID 178478124HCID 178478124, compound

Product 1

HCID 71471734HCID 71471734, compound

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-bromo-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one (40 mg, 0.10 mmol) in THF (0.4 mL) at 0° C. was added (2-chloro-5-pyridyl)methylzinc chloride (0.5 M in THF, 408 μL, 0.20 mmol) and Pd(PtBu3)2. The mixture was warmed to rt and stirred for 30 min. The resulting solution was quenched with water and extracted with CH2Cl2. The combined extracts were dried (Na2SO4) and concentrated. Purification by silica gel chromatography (0-5% MeOH/CH2Cl2) afforded 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one in pure form: 1H NMR (400 MHz, CD3OD); 1H NMR (400 MHz, CDCl3) 8.20 (d, J=2.3 Hz, 1H), 8.03 (s, 1H), 7.59 (s, 1H), 7.33 (dd, J=2.3, 8.2 Hz, 1H), 7.17 (d, J=8.2 Hz, 1H), 4.51 (m, 1H), 3.96 (s, 2H), 3.90 (m, 1H), 3.12 (t, J=5.2 Hz, 2H), 3.08 (s, 3H), 2.56 (t, J=6.5 Hz, 2H), 2.24-2.15 (m, 2H), 2.00-1.92 (m, 2H), 1.89-1.75 (m, 4H), 1.55-1.37 (m, 2H); HRMS (MH+) calcd for C24H28ClN4O2 439.1895. found 439.1894.

Workup

  1. customThe resulting solution was quenched with water
  2. extractionextracted with CH2Cl2
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-6d8db76fead54a209f70badc2adbf36c
Source dataset
uspto-grants-2016_03
Patent number
US09284312B2

Reaction notes

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