Formic Acid → 4-(3,5-Dichloro-pyridin-4-ylmethyl)-7-methoxy-1H-phthalazin-2-carbaldehyde

HRID 2268848Notes

Reaction equation

HRID 2268848 reaction equation
[CH:1]([OH:3])=O.N#N.C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl:18][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:38])[C:24]=1[CH2:25][C:26]1[C:35]2[C:30](=[CH:31][C:32]([O:36][CH3:37])=[CH:33][CH:34]=2)[CH2:29][NH:28][N:27]=1.C(O)=O.C(N1C=CN=C1)(N1C=CN=C1)=O>C1COCC1>[Cl:18][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([Cl:38])[C:24]=1[CH2:25][C:26]1[C:35]2[C:30](=[CH:31][C:32]([O:36][CH3:37])=[CH:33][CH:34]=2)[CH2:29][N:28]([CH:1]=[O:3])[N:27]=1

Participants

7

Reactant 5

HCID 284Formic AcidHCID 947NitrogenHCID 682631,1'-CarbonyldiimidazoleHCID 9797215Phthalazine, 4-[(3,5-dichloro-4-pyridinyl)methyl]-1,2-dihydro-7-methoxy-HCID 131723010HCID 131723010, compound

Product 1

HCID 183816464-(3,5-Dichloro-pyridin-4-ylmethyl)-7-methoxy-1H-phthalazin-2-carbaldehydeYield 92.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of formic acid (0.123 ml, 3.255 mmoles) in dry THF (40 ml), under stirring and dry N2 at room temperature, was added with 1,1′-carbonyldiimidazole (0.53 g, 3.255 mmoles) and the mixture was left to stand for 1 hour. Then 4-(3,5-dichloro-pyridin-4-ylmethyl)-7-methoxy-1,2-dihydro-phthalazine (1 g, 3.1 mmoles), prepared as described in example 22, was portionwise added. After 6.5 hours another portion of a mixture of formic acid/carbonyldiimidazole (about ⅓ of the previous one) was added and the mixture was stirred at room temperature for 1 hour, then left to stand overnight. The mixture was poured into water/ice, THF was evaporated, and the solution was extracted more times with CH2Cl2. The organic phase was washed with KHSO4, then with NaHCO3 and with water, anhydrified and concentrated. The residue was crystallised from acetonitrile (40 ml) to give 1 g of the title compound (yield: 92.6%). m.p.: 165-167° C.

Workup

  1. waitthe mixture was left
  2. additionwas portionwise added
  3. additionwas added
  4. waitleft
  5. waitto stand overnight
  6. customwas evaporated
  7. extractionthe solution was extracted more times with CH2Cl2
  8. washThe organic phase was washed with KHSO4
  9. concentrationwith NaHCO3 and with water, anhydrified and concentrated
  10. customThe residue was crystallised from acetonitrile (40 ml)

Sources & evidence

ORD record
ord-6e1c3dee34ae40258fcc3ca4e879550d
Source dataset
uspto-grants-2001_12
Patent number
US06329370B1

Reaction notes

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