Sodium hydride → HCID 56643913, compound

HRID 595138Notes

Reaction equation

HRID 595138 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]([CH3:15])[C:13](=[O:16])[C:12]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][N:18]=3)=[CH:11][N:10]=2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:27]1[C:28]2[CH:29]=[C:30]3[O:46][CH2:45][CH2:44][O:43][CH2:42][CH2:41][O:40][CH2:39][CH2:38][O:37][C:31]3=[CH:32][C:33]=2[N:34]=[CH:35][N:36]=1>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]([CH3:15])[C:13](=[O:16])[C:12]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:27]4[C:28]5[CH:29]=[C:30]6[O:46][CH2:45][CH2:44][O:43][CH2:42][CH2:41][O:40][CH2:39][CH2:38][O:37][C:31]6=[CH:32][C:33]=5[N:34]=[CH:35][N:36]=4)=[CH:19][N:18]=3)=[CH:11][N:10]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 446082034-Chloro-7,8,10,11,13,14-hexahydro-[1,4,7,10]tetraoxacyclododecino[2,3-g]quinazolineHCID 68297825HCID 68297825, compound

Product 1

HCID 56643913HCID 56643913, compoundYield 93.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-(4-Fluoro-phenylamino)-5-(5-hydroxy-pyridin-2-yl)-3-methyl-3H-pyrimidin-4-one (2.18 g, 7 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 and further purification to yield product (3.68 g, 90%). 1HNMR (400 MHz, DMSO): 9.18 (s, 1H), 8.60 (m, 3H), 8.45 (d, 1H), 7.84 (s, 1H), 7.82 (m, 1H), 7.55 (m, 3H), 7.21 (m, 2H), 4.35 (s, 4H), 3.87 (d, 4H), 3.62 (s, 4H). LC/MS Calcd for (M+H)+587.6. found 587.9.

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
  6. customto give
  7. customcrude title compound and further purification

Sources & evidence

ORD record
ord-50e47dcc261e430fbdf2f553e27b95d7
Source dataset
uspto-grants-2016_01
Patent number
US09242991B2

Reaction notes

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