Tert-Butylamine → HCID 178449350, compound

HRID 526523Notes

Reaction equation

HRID 526523 reaction equation
C1C=CC2N(O)N=NC=2C=1.[C:11]([C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:20]=[N:21][N:22]([C:25]3[CH:33]=[CH:32][C:28]([C:29]([OH:31])=O)=[CH:27][N:26]=3)[C:23]=2[OH:24])=[CH:15][CH:14]=1)#[N:12].[C:34]([NH2:38])([CH3:37])([CH3:36])[CH3:35].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O.CS(C)=O.C(Cl)CCl>[C:34]([NH:38][C:29](=[O:31])[C:28]1[CH:32]=[CH:33][C:25]([N:22]2[C:23]([OH:24])=[C:19]([C:16]3[CH:15]=[CH:14][C:13]([C:11]#[N:12])=[CH:18][CH:17]=3)[CH:20]=[N:21]2)=[N:26][CH:27]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

10

Reactant 5

HCID 6385Tert-Butylamine2×HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178509615HCID 178509615, compound

Product 1

HCID 178449350HCID 178449350, compoundYield 16.77%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolvent2×HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combined EDC (45.1 mg, 0.235 mmol), HOBT (21.18 mg, 0.157 mmol) and 6-(4-(4-cyanophenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (48 mg, 0.157 mmol) in DMF (1 mL) then added tert-butylamine (0.050 mL, 0.470 mmol) and Hunig's base (0.082 mL, 0.470 mmol) and then stirred at 20° C. for 21 h. Addition EDC (45 mg) and tert-butyl amine (100 uL) were then added and stirring continued at 20° C. for 4 h. Then additional HATU (119 mg, 0.313 mmol) was added and stirring continued at 20° C. for 2 h. The reaction mixture was then diluted with EtOAc (50 mL), washed with saturated aqueous ammonium chloride (50 mL) and brine, dried over magnesium sulfate, and concentrated in vacuo to give a residue which was dissolved in DMSO (1 mL) and purified by prep HPLC (ACN/water with formic acid) to give the title compound (9.5 mg, 16.77% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.34 (s, 9H) 7.72 (d, J=8.3 Hz, 2H) 7.98 (s, 1H) 8.07 (br. s., 2H) 8.33 (d, J=7.3 Hz, 2H) 8.58 (br. s., 1H) 8.79 (s, 1H) 13.48 (br. s., 1H). MS m/z 362 [M+H]+.

Workup

  1. additionwere then added
  2. stirringstirring
  3. waitcontinued at 20° C. for 2 h
  4. washwashed with saturated aqueous ammonium chloride (50 mL) and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a residue which
  8. custompurified by prep HPLC (ACN/water with formic acid)

Sources & evidence

ORD record
ord-f7a8b95a383440029055ccf2a7f761fe
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Reaction notes

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