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 1428206ノート

反応式

HRID 1428206 の反応式
[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]

参加物

7

反応物 3

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2 回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

生成物 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}-amide収率 19%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-f406bdba2d9345cc9432fc1acdcae42e
出典データセット
uspto-grants-2015_01
特許番号
US08937073B2

反応ノート

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