O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → (S)-6-oxo-1,6-dihydro-pyridazine-4-carboxylic acid-{3-[2-fluoro-4-(4-methoxy-2-tri-fluoromethyl-phenylamino)-benzylcarbamoyl]-tetrahydrofuran-3-yl}-amide

HRID 1428206Notes

Reaction equation

HRID 1428206 reaction equation
[O:1]=[C:2]1[NH:7][N:6]=[CH:5][C:4]([C:8]([NH:10][C@@:11]2([C:16]([OH:18])=O)[CH2:15][CH2:14][O:13][CH2:12]2)=[O:9])=[CH:3]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:41][C:42]1[CH:49]=[C:48]([NH:50][C:51]2[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][C:52]=2[C:59]([F:62])([F:61])[F:60])[CH:47]=[CH:46][C:43]=1[CH2:44][NH2:45]>O1CCCC1.CN(C=O)C.C(N(CC)CC)C>[F:41][C:42]1[CH:49]=[C:48]([NH:50][C:51]2[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][C:52]=2[C:59]([F:60])([F:61])[F:62])[CH:47]=[CH:46][C:43]=1[CH2:44][NH:45][C:16]([C@:11]1([NH:10][C:8]([C:4]2[CH:5]=[N:6][NH:7][C:2](=[O:1])[CH:3]=2)=[O:9])[CH2:15][CH2:14][O:13][CH2:12]1)=[O:18]

Participants

7

Reactant 3

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2×HCID 59496525(S)-3-[(6-oxo-1,6-dihydro-pyridazine-4-carbonyl)-amino]-tetrahydrofuran-3-carboxylic acidHCID 667658162-Fluoro-4-(4-methoxy-2-trifluoromethyl-phenylamino)-benzylamine

Product 1

HCID 56837587(S)-6-oxo-1,6-dihydro-pyridazine-4-carboxylic acid-{3-[2-fluoro-4-(4-methoxy-2-tri-fluoromethyl-phenylamino)-benzylcarbamoyl]-tetrahydrofuran-3-yl}-amideYield 19%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

(S)-3-[(6-oxo-1,6-dihydro-pyridazine-4-carbonyl)-amino]-tetrahydrofuran-3-carboxylic acid (0.55 mmol) was dissolved in a mixture of 30 mL tetrahydrofuran, 4 mL DMF and 0.15 mL triethylamine, then TBTU (0.19 g, 0.58 mmol) was added and the mixture was stirred for 30 minutes at ambient temperature. Then 2-fluoro-4-(4-methoxy-2-trifluoromethyl-phenylamino)-benzylamine (0.17 g, 0.55 mMol, from 1b) was added and the mixture was stirred for a further two hours. As there was still some unreacted amine present, another 10 mg of the acid and 20 mg TBTU were added and the mixture was stirred further overnight. Then the solvents were evaporated off and the residue was chromatographed on silica gel (eluant: dichloromethane/methanol/ammonia: 95/5/0.5). In this way the product was obtained in a yield of 19% of theory.

Workup

  1. stirringthe mixture was stirred for a further two hours
  2. stirringthe mixture was stirred further overnight
  3. customThen the solvents were evaporated off
  4. customthe residue was chromatographed on silica gel (eluant: dichloromethane/methanol/ammonia: 95/5/0.5)
  5. customIn this way the product was obtained in a yield of 19% of theory

Sources & evidence

ORD record
ord-f406bdba2d9345cc9432fc1acdcae42e
Source dataset
uspto-grants-2015_01
Patent number
US08937073B2

Reaction notes

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