Sulfuric Acid → HCID 46831861, compound

HRID 2368786Notes

Reaction equation

HRID 2368786 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C@@H:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([NH:19][C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([NH:27][C:28]5[N:33]=[C:32]([C:34]6[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=6)[CH:31]=[CH:30][N:29]=5)[CH:21]=4)=[O:18])=[CH:14][CH:15]=3)[CH2:10][CH2:9]2)[CH2:4][CH2:3]1.[S:40](=[O:44])(=[O:43])([OH:42])[OH:41]>C(O)C>[S:40]([OH:44])([OH:43])(=[O:42])=[O:41].[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C@@H:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([NH:19][C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([NH:27][C:28]5[N:33]=[C:32]([C:34]6[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=6)[CH:31]=[CH:30][N:29]=5)[CH:21]=4)=[O:18])=[CH:14][CH:15]=3)[CH2:10][CH2:9]2)[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 46831579HCID 46831579, compound

Product 1

HCID 46831861HCID 46831861, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

(1S)-1-(4-Methylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-Dihydro-1H-indene-5-carboxamide (248 g, 0.477 mol) was dissolved in ethanol (4.76 L). After being stirred for 20 minutes, the solution was filtered with suction. The filtrate was added to a 20 L three-neck flask. Sulfuric acid solution (46.74 g, 0.477 mol, 1-fold) diluted with ethanol (532 ml) was added slowly through dropping funnel with thorough stirring to form a yellowish suspension. Ethanol (9.5 L) was then supplemented. The mixture was heated under reflux for 2 hours until it became a milky-white suspension. The suspension was cooled to room temperature statically, filtered with suction, and then dried to obtain the title product (183 g, 57.5%). The filtrate was adjusted to basic (pH=11) with aqueous solution of NaOH and then extracted with methylene dichloride (4×200 mL). The extract was dried and concentrated to reclaim the (1S)-1-(4-methyl piperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-inden e-5-carboxamide (98 g, 39.5%). Melting point of the title product: 187˜189° C. Elemental analysis of C31H36N7O7S1.5, calculating value: C, 55.84; H, 5.44; N, 14.71; testing value: C, 55.72; H, 5.70; N, 14.40.

Workup

  1. filtrationthe solution was filtered with suction
  2. additionThe filtrate was added to a 20 L three-neck flask
  3. additionwas added slowly
  4. stirringwith thorough stirring
  5. customto form a yellowish suspension
  6. temperatureThe mixture was heated
  7. temperatureunder reflux for 2 hours until it
  8. filtrationfiltered with suction
  9. customdried

Sources & evidence

ORD record
ord-f42b350901b340ce8aad163099a736cb
Source dataset
uspto-grants-2014_04
Patent number
US08703771B2

Reaction notes

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