1-Hydroxybenzotriazole → HCID 57542846, compound

HRID 2080301Notes

Reaction equation

HRID 2080301 reaction equation
[F:1][C:2]1[C:3]([C:21]2[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=2)=[N:4][C:5]([NH:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[C:6]([CH:10]=1)[C:7](O)=[O:8].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[NH2:61][CH2:62][C@H:63]1[CH2:66][CH2:65][N:64]1[C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68].CCN(C(C)C)C(C)C>CN(C=O)C>[F:1][C:2]1[C:3]([C:21]2[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=2)=[N:4][C:5]([NH:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[C:6]([CH:10]=1)[C:7]([NH:61][CH2:62][C@H:63]1[CH2:66][CH2:65][N:64]1[C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])=[O:8]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 51557285HCID 51557285, compoundHCID 57542598HCID 57542598, compound

Product 1

HCID 57542846HCID 57542846, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 5-fluoro-2-(3-fluorophenethylamino)-6-(1-methyl-1H-pyrazol-4-yl)nicotinic acid (14.3 g, 40 mmol) and DMF (300 mL) was added of HBTU (18.2 g, 48 mmol) and HOBT (6.49 g, 48 mmol). The mixture was cooled down to 0° C., 8.93 g (48 mmol) of (R)-tert-butyl 2-(aminomethyl)azetidine-1-carboxylate was added, followed by 13.9 ml of DIEA (80 mmol). The mixture was stirred at r.t for 1 hour and extracted with 300 mL EtOAc. The organic layer was washed with 500 mL brine, dried over MgSO4 and then concentrated. The residue was purified by Biotage silica gel chromatography using EtOAc:Hex (1:1) as eluant. (R)-tert-butyl 2-((5-fluoro-2-(3-fluorophenethylamino)-6-(1-methyl-1H-pyrazol-4-yl)nicotinamido)methyl)azetidine-1-carboxylate was obtained as a yellow solid (16.5 g, yield 80%). LRMS (M+H+) m/z 527.1.

Workup

  1. extractionextracted with 300 mL EtOAc
  2. washThe organic layer was washed with 500 mL brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by Biotage silica gel chromatography

Sources & evidence

ORD record
ord-40f9b29587e440c1b8808e416219e7fa
Source dataset
uspto-grants-2011_04
Patent number
US07932270B2

Reaction notes

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