Tert-Butylamine → N-tert-Butyl-6-((4-(4-(3-cyclobutylureido)-3-fluorobenzoyl)piperazin-1-yl)methyl)picolinamide

HRID 408878Notes

Reaction equation

HRID 408878 reaction equation
[CH:1]1([NH:5][C:6](=[O:33])[NH:7][C:8]2[CH:31]=[CH:30][C:11]([C:12]([N:14]3[CH2:19][CH2:18][N:17]([CH2:20][C:21]4[N:26]=[C:25]([C:27]([O-:29])=O)[CH:24]=[CH:23][CH:22]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:10][C:9]=2[F:32])[CH2:4][CH2:3][CH2:2]1.[Na+].C(N(CC)CC)C.[C:42]([NH2:46])([CH3:45])([CH3:44])[CH3:43].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl>[C:42]([NH:46][C:27](=[O:29])[C:25]1[CH:24]=[CH:23][CH:22]=[C:21]([CH2:20][N:17]2[CH2:18][CH2:19][N:14]([C:12](=[O:13])[C:11]3[CH:30]=[CH:31][C:8]([NH:7][C:6]([NH:5][CH:1]4[CH2:4][CH2:3][CH2:2]4)=[O:33])=[C:9]([F:32])[CH:10]=3)[CH2:15][CH2:16]2)[N:26]=1)([CH3:45])([CH3:44])[CH3:43]

Participants

6

Reactant 4

HCID 6385Tert-ButylamineHCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 66661327Sodium 6-((4-(4-(3-cyclobutylureido)-3-fluorobenzoyl)piperazin-1-yl)methyl)picolinate

Product 1

HCID 46182303N-tert-Butyl-6-((4-(4-(3-cyclobutylureido)-3-fluorobenzoyl)piperazin-1-yl)methyl)picolinamideYield 22.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Sodium 6-((4-(4-(3-cyclobutylureido)-3-fluorobenzoyl)piperazin-1-yl)methyl)-picolinate (100 mg, 0.209 mmol), triethylamine (66 mg, 0.693 mmol, 0.091 mL) and tert-butylamine (32 mg, 0.435 mmol) were combined and stirred at room temperature in dichloromethane. 1-Propanephosphonic acid cyclic anhydride (208 mg, 0.326 mmol, 0.194 mL, 50% solution in ethyl acetate) was added dropwise and the reaction allowed to stir for 1 hour. The reaction mixture was concentrated at reduced pressure, the resulting residue taken up in ethyl acetate and washed with saturated sodium bicarbonate solution. The organic phase was dried over sodium sulfate and concentrated under vacuum to afford the title compound (24 mg). MS (ESI) m/z 511.6 [M+H]+

Workup

  1. concentrationThe reaction mixture was concentrated at reduced pressure
  2. washwashed with saturated sodium bicarbonate solution
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-4a47a204cc7e4ab2b1656a16b64f2ac7
Source dataset
uspto-grants-2014_06
Patent number
US08759352B2

Reaction notes

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