1-Hydroxybenzotriazole → HCID 68514173, compound

HRID 2241285Notes

Reaction equation

HRID 2241285 reaction equation
[CH3:1][O:2][C:3]1[CH:40]=[CH:39][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10]([C:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH:27]=3)=[N:9]2)=[CH:5][CH:4]=1.[F:41][C:42]1[CH:47]=[CH:46][C:45]([N:48]2[C:53](=[O:54])[C:52]([C:55](O)=[O:56])=[CH:51][CH:50]=[N:49]2)=[CH:44][CH:43]=1.Cl.C(N=C=NCCCN(C)C)C.N1(O)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C>[F:25][C:19]1[CH:20]=[C:21]([NH:24][C:55]([C:52]2[C:53](=[O:54])[N:48]([C:45]3[CH:46]=[CH:47][C:42]([F:41])=[CH:43][CH:44]=3)[N:49]=[CH:50][CH:51]=2)=[O:56])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:40][CH:39]=3)[N:9]=[C:10]([C:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[CH2:28][CH:27]=3)[C:11]=12

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 667671712-(4-Fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acidHCID 68516875HCID 68516875, compound

Product 1

HCID 68514173HCID 68514173, compoundYield 54.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 50 mL round-bottomed flask was charged with tert-butyl 4-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate (50.0 mg, 0.0916 mmol), 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (42.9 mg, 0.183 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (52.7 mg, 0.275 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (37.1 mg, 0.275 mmol), N-ethyl-N-isopropylpropan-2-amine (0.0818 ml, 0.458 mmol) and DMF (5 mL). The reaction mixture was stirred at room temperature until LC-MS showed that the starting material had been consumed (2 days). The reaction was partitioned between EtOAc and H2O. The phases were separated and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (38.3 mg, 54.9%). LRMS (APCI pos) m/e 662 (M−99).

Workup

  1. customhad been consumed (2 days)
  2. customThe reaction was partitioned between EtOAc and H2O
  3. customThe phases were separated
  4. extractionthe aqueous phase was re-extracted with EtOAc
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude product
  9. customThe crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1

Sources & evidence

ORD record
ord-fcd56b59682044c7ba4f45f0c9a12aa3
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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