Sodium Bicarbonate → HCID 9890142, compound

HRID 2100384Notes

Reaction equation

HRID 2100384 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[C:9]([F:43])[C:10]([CH3:42])=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([NH:21][CH2:22][C:23](C)([CH3:25])[CH3:24])=[O:20])=[CH:15][C:14]=3[O:27][CH2:28][CH2:29]CC(NNC(OC(C)(C)C)=O)=O)[CH:12]=2)=[O:6])[CH2:3][CH2:2]1.[CH:44]1([NH:47][C:48](=O)C2C=C(F)C(C)=C(B3OC(C)(C)C(C)(C)O3)C=2)CC1.C(=O)([O-])O.[Na+]>CC(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([NH:4][C:5]([C:7]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([NH:21][CH2:22][CH:23]4[CH2:24][CH2:25]4)=[O:20])=[CH:15][C:14]=3[O:27][CH2:28][CH2:29][N:47]([CH3:48])[CH3:44])[C:10]([CH3:42])=[C:9]([F:43])[CH:8]=2)=[O:6])[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 68829345HCID 68829345, compound2×

Product 1

HCID 9890142HCID 9890142, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 3776IsopropanolSolvent

Procedure

N-Cyclopropylmethyl-3-[2-(dimethylarnino)ethoxy]4-iodobenzamide (Intermediate 1) (42 mg), N-cyclopropyl-5-fluoro-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (38 mg), tetrakis(triphenylphosphine)palladium (2 mg) and aqueous sodiumhydrogen carbonate (1M, 0.3 ml) were reacted in propan-2-ol (2 ml) at 9° C. for 20 hours. The solvent was evaporated under vacuum and the residue purified by bond-elut (silica, 10 g) eluting with a methanol/chloroform gradient (1-10% methanol) to give, after evaporation of the solvents, N3-cyclopropyl-N4′-(cyclopropylmethyl)-2′-[2-(dimethylamino)ethoxy]-5-fluoro-6-methyl-1,1 ′-biphenyl-3,4′-dicarboxamide.

Workup

  1. customThe solvent was evaporated under vacuum
  2. customthe residue purified by bond-elut (silica, 10 g)
  3. washeluting with a methanol/chloroform gradient (1-10% methanol)
  4. customto give
  5. customafter evaporation of the solvents, N3-cyclopropyl-N4′-(cyclopropylmethyl)-2′-[2-(dimethylamino)ethoxy]-5-fluoro-6-methyl-1,1 ′-biphenyl-3,4′-dicarboxamide

Sources & evidence

ORD record
ord-b1bab730d178411ca90cb5e7472c1b29
Source dataset
uspto-grants-2009_08
Patent number
US07572790B2

Reaction notes

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