2-Chloro-6-fluorobenzoic acid → HCID 178497001, compound

HRID 1898335Notes

Reaction equation

HRID 1898335 reaction equation
[NH2:1][C:2]1[NH:6][C:5]2[C:7]3[CH2:8][C:9]([CH3:19])([CH3:18])[O:10][C:11]=3[C:12]([C:14]([O:16][CH3:17])=[O:15])=[CH:13][C:4]=2[N:3]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[Cl:42][C:43]1[CH:51]=[CH:50][CH:49]=[C:48]([F:52])[C:44]=1[C:45](O)=[O:46]>C1COCC1>[Cl:42][C:43]1[CH:51]=[CH:50][CH:49]=[C:48]([F:52])[C:44]=1[C:45]([NH:1][C:2]1[NH:6][C:5]2[C:7]3[CH2:8][C:9]([CH3:19])([CH3:18])[O:10][C:11]=3[C:12]([C:14]([O:16][CH3:17])=[O:15])=[CH:13][C:4]=2[N:3]=1)=[O:46]

Participants

6

Reactant 4

HCID 679472-Chloro-6-fluorobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178497007HCID 178497007, compound

Product 1

HCID 178497001HCID 178497001, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-amino-7,7-dimethyl-7,8-dihydro-1H-benzofuro[4,5-d]imidazole-5-carboxylate (1.00 g, 3.81 mmol) in THF (25 mL) was added EDCI.HCl (1.4 g, 7.62 mmol), HOBT (1.00 g, 7.62 mmol), 2-chloro-6-fluorobenzoic acid (1.32 g 7.62 mmol) and TEA (3 mL). The reaction mass was stirred for 18 h. The reaction mass was quenched in water extracted with 10% DCM: methanol. The organic layer was dried over anhydrous sodium sulphate and concentrated. The obtained crude was purified by column chromatography on basic alumina eluting with 0.7% DCM: MeOH to afford 0.700 g of the desired product. 1HNMR (DMSO-d6): δ 1.43 (s, 6H), 3.02 (s, 2H), 3.58 (s, 3H), 6.08 (bs, 1H), 7.59-7.69 (m, 2H), 7.83 (q, J=6.6 Hz, 1H), 8.14 (bs, 2H); MS [M+H]+: 418.05.

Workup

  1. customThe reaction mass was quenched in water
  2. extractionextracted with 10% DCM
  3. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  4. concentrationconcentrated
  5. customThe obtained crude
  6. customwas purified by column chromatography on basic alumina eluting with 0.7% DCM

Sources & evidence

ORD record
ord-022176e27aff4db89bc1ac7ca7883710
Source dataset
uspto-grants-2013_08
Patent number
US08519149B2

Reaction notes

Loading…