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 1428206노트

반응식

HRID 1428206 반응식
[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]

참가 물질

7

반응물 3

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2회HCID 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

생성물 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}-amide수율 19%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매

실험 절차

(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.

후처리

  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

출처 및 근거

ORD 기록
ord-f406bdba2d9345cc9432fc1acdcae42e
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08937073B2

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