Sodium Bicarbonate → HCID 90109738, compound

HRID 521726Notes

Reaction equation

HRID 521726 reaction equation
ClC(N(C)C)=C(C)C.[F:9][C:10]1[C:11]([O:42][CH3:43])=[N:12][C:13]([N:17]2[CH2:21][CH:20]([CH2:22]O)[C:19]([NH:30][C:31]([NH:33][C:34](=[O:41])[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[S:32])([C:24]3[CH:29]=[N:28][CH:27]=[CH:26][N:25]=3)[CH2:18]2)=[N:14][C:15]=1[CH3:16].C(=O)(O)[O-].[Na+]>ClCCl>[F:9][C:10]1[C:11]([O:42][CH3:43])=[N:12][C:13]([N:17]2[CH2:21][CH:20]3[C:19]([C:24]4[CH:29]=[N:28][CH:27]=[CH:26][N:25]=4)([N:30]=[C:31]([NH:33][C:34](=[O:41])[C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[S:32][CH2:22]3)[CH2:18]2)=[N:14][C:15]=1[CH3:16]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 90111324HCID 90111324, compound

Product 1

HCID 90109738HCID 90109738, compoundYield 64.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-Chloro-N,N,2-trimethylpropenylamine (492 μL, 3.71 mmol) is added to a stirred solution of N-[[1-(5-fluoro-4-methoxy-6-methyl-pyrimidin-2-yl)-4-(hydroxymethyl)-3-pyrazin-2-yl-pyrrolidin-3-yl]carbamothioyl]benzamide (1.32 g, 2.65 mmol) in dichloromethane (30 mL) at room temperature. The reaction mixture is stirred for 1 hour 30 minutes. Then a saturated aqueous solution of sodium bicarbonate (20 mL) is added followed by dichloromethane (70 mL). The layers are separated and the aqueous layer is re-extracted with dichloromethane (70 mL). The combined organic layers are dried over magnesium sulfate and the solvent is evaporated under reduced pressure. The resulting residue is dissolved in methanol (40 mL) and loaded on an ion exchange column. The column is eluted with methanol (60 mL) then with 7 M ammonia/methanol solution (100 mL). The basic solvent fraction is collected and evaporated under reduced pressure. The isolated residue is further purified by silica gel column chromatography using a 0-5% gradient of 0.14 M ammonia/methanol solution in dichloromethane to give the title compound (820 mg, 64%). ES/MS (m/e): 480 (M+1).

Workup

  1. customThe layers are separated
  2. extractionthe aqueous layer is re-extracted with dichloromethane (70 mL)
  3. dry with materialThe combined organic layers are dried over magnesium sulfate
  4. customthe solvent is evaporated under reduced pressure
  5. dissolutionThe resulting residue is dissolved in methanol (40 mL)
  6. washThe column is eluted with methanol (60 mL)
  7. customThe basic solvent fraction is collected
  8. customevaporated under reduced pressure
  9. customThe isolated residue is further purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6a34c4bcf3a24315a64b5eeb545a98c4
Source dataset
uspto-grants-2016_05
Patent number
US09328124B2

Reaction notes

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