Nicotinic Acid → HCID 178488374, compound

HRID 536222Notes

Reaction equation

HRID 536222 reaction equation
[CH3:1][O:2][C:3]1[C:12]2[N:11]=[C:10]([NH2:13])[N:9]3[CH2:14][CH2:15][N:16]=[C:8]3[C:7]=2[CH:6]=[CH:5][CH:4]=1.[C:17](O)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[N:20][CH:19]=1.C(N(C(C)C)CC)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:1][O:2][C:3]1[C:12]2[N:11]=[C:10]([NH:13][C:17](=[O:24])[C:18]3[CH:23]=[CH:22][CH:21]=[N:20][CH:19]=3)[N:9]3[CH2:14][CH2:15][N:16]=[C:8]3[C:7]=2[CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 938Nicotinic AcidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 178488375HCID 178488375, compound

Product 1

HCID 178488374HCID 178488374, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7-Methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-amine (Step 4, 31.2 g, 57.7 mmol), nicotinic acid (10.7 g, 86 mmol) and diisopropylethylamine (30.1 mL, 173 mmol) were suspended in DMF (250 mL), and PyBOP (45 g, 86 mmol) was added portionwise. The reaction soon became much thicker with a new solid. After stirring overnight, the solid was collected by filtration then washed with EtOAc (150 mL). The solid was dissolved in CH2Cl2 (1000 mL), washed with water (600 mL) and the organic layer dried over Na2SO4. The solvent was removed under reduced pressure to give the title compound (12.6 g, 68%): HPLC MS RT=1.18 min, MH+=322.1; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 4.12 (3H, s), 4.28-4.35 (2H, m), 4.60-4.66 (2H, m), 7.63 (1H, t), 7.72-7.86 (3H, m), 8.76 (1H, d), 8.93 (1H, dd), 9.48 (1H, d).

Workup

  1. customThe reaction
  2. filtrationthe solid was collected by filtration
  3. washthen washed with EtOAc (150 mL)
  4. dissolutionThe solid was dissolved in CH2Cl2 (1000 mL)
  5. washwashed with water (600 mL)
  6. dry with materialthe organic layer dried over Na2SO4
  7. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-9d2e9468f0a645dba17f4ee7c327e0b6
Source dataset
uspto-grants-2014_10
Patent number
US08859572B2

Reaction notes

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