Dimethylformamide → 4-(4-Amino-2-Methyl-phenoxy)-7,8,10,11,13,14-hexahydro-6,9,12,15-tetraoxa-1,3-diaza-cyclododeca[b]naphthalene

HRID 595136Notes

Reaction equation

HRID 595136 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4](F)[CH:3]=1.[H-].[Na+].Cl[C:13]1[C:14]2[CH:15]=[C:16]3[O:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27][O:26][CH2:25][CH2:24][O:23][C:17]3=[CH:18][C:19]=2[N:20]=[CH:21][N:22]=1.[CH3:33]N(C=O)C>CCOC(C)=O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:13]2[C:14]3[CH:15]=[C:16]4[O:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27][O:26][CH2:25][CH2:24][O:23][C:17]4=[CH:18][C:19]=3[N:20]=[CH:21][N:22]=2)=[C:4]([CH3:33])[CH:3]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 2735918Phenol, 4-amino-2-fluoro-HCID 446082034-Chloro-7,8,10,11,13,14-hexahydro-[1,4,7,10]tetraoxacyclododecino[2,3-g]quinazoline

Product 1

HCID 866848304-(4-Amino-2-Methyl-phenoxy)-7,8,10,11,13,14-hexahydro-6,9,12,15-tetraoxa-1,3-diaza-cyclododeca[b]naphthaleneYield 100%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4-amino-2-fluoro-phenol (1.53 g, 12.0 mmol) was dissolved in dry DMF (30 ml) to which was added 60% NaH (774 mg, 19.3 mmol). After the mixture was stirred at room temperature for several minutes, a suspension of 4-Chloro-7,8,10,11,13,14-hexahydro-6,9,12,15-tetraoxa-1,3-diaza-cyclododeca[b]naphthalene (2.08 g, 6.7 mmol) in dry DMF (40 ml) was added. The reaction mixture was stirred at room temperature for 1-2 hrs, then diluted with EtOAc and washed with sat'd NaHCO3 (3×), H2O (1×), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo to give crude title compound (2.68 g, −100%) which was used in the next reaction without further purification. 1H-NMR (400 MHz, DMSO): 8.58 (s, 1H), 7.80 (s, 1H), 7.50 (s, 1H), 7.04 (t, 1H), 6.50 (dd, 2H), 5.40 (br s, 2H), 4.35 (s, 4H), 3.87 (d, 4H), 3.62 (s, 4H). LC/MS Calcd for (M+H)′ 401.4. found 402.5.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at room temperature for 1-2 hrs
  3. washwashed with sat'd NaHCO3 (3×), H2O (1×), sat'd NaCl (1×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bb138c4904ad45c7b0ea69508c7ac01a
Source dataset
uspto-grants-2016_01
Patent number
US09242991B2

Reaction notes

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