Acetone → 3-[2-{[3-(Diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-n-propylbenzamide phosphate salt

HRID 2243682Notes

Reaction equation

HRID 2243682 reaction equation
CC(C)=O.[CH2:5]([N:7]([CH2:44][CH3:45])[CH2:8][CH2:9][CH2:10][NH:11][C:12]1[N:13]=[C:14]([C:31]2[CH:32]=[C:33]([CH:40]=[CH:41][C:42]=2[CH3:43])[C:34]([NH:36][CH2:37][CH2:38][CH3:39])=[O:35])[C:15]2[CH2:20][NH:19][C:18](=[O:21])[N:17]([C:22]3[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=3[F:29])[C:16]=2[N:30]=1)[CH3:6].[P:46](=[O:50])([OH:49])([OH:48])[OH:47]>CO>[P:46]([OH:50])([OH:49])([OH:48])=[O:47].[CH2:44]([N:7]([CH2:5][CH3:6])[CH2:8][CH2:9][CH2:10][NH:11][C:12]1[N:13]=[C:14]([C:31]2[CH:32]=[C:33]([CH:40]=[CH:41][C:42]=2[CH3:43])[C:34]([NH:36][CH2:37][CH2:38][CH3:39])=[O:35])[C:15]2[CH2:20][NH:19][C:18](=[O:21])[N:17]([C:22]3[C:23]([F:29])=[CH:24][CH:25]=[CH:26][C:27]=3[F:28])[C:16]=2[N:30]=1)[CH3:45]

Participants

5

Reactant 3

HCID 180AcetoneHCID 1004Phosphoric AcidHCID 119499263-[2-{[3-(diethylamino)propyl]-amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide

Product 1

HCID 685867043-[2-{[3-(Diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-n-propylbenzamide phosphate saltYield 67.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
50 °C

Procedure

Acetone (845 uL) was added to the crystalline 3-[2-{[3-(diethylamino)propyl]-amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide-free-base (46.9 mg), and the resulting mixture was heated to 50° C. Phosphoric acid was added (1.0 equivalents; 1M in methanol). Additional methanol (5 uL) was added to the resulting oily mixture to increase solubility slightly. The mixture was cooled to room temperature and stirred overnight. The product was filtered and dried for at least one hour in a vacuum oven at 50° C. with a slow nitrogen bleed. The yield was 67.1% (36.9 mg) of partially crystalline 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide phosphate salt.

Workup

  1. temperatureto increase solubility slightly
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationThe product was filtered
  4. customdried for at least one hour in a vacuum oven at 50° C. with a slow nitrogen

Sources & evidence

ORD record
ord-6fecc32ad0f24778aa02c3f7010509a4
Source dataset
uspto-grants-2010_03
Patent number
US07674789B2

Reaction notes

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