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 fumarate salt

HRID 2243681Notes

Reaction equation

HRID 2243681 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].[C:46]([OH:53])(=[O:52])/[CH:47]=[CH:48]/[C:49]([OH:51])=[O:50]>O>[C:46]([OH:53])(=[O:52])/[CH:47]=[CH:48]/[C:49]([OH:51])=[O:50].[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 444972Fumaric 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 685873683-[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 fumarate saltYield 85.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Acetone with 5% water (12.2 mL) 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 (0.608 g) and solid fumaric acid (1.0 equivalents; 124.8 mg). The resulting mixture was heated to 50° C. for one hour. The mixture was cooled to room temperature and stirred for 30 minutes. The product was filtered, washed with acetone with 5% water, and dried overnight in a vacuum oven at 50° C. with a slow nitrogen bleed. The yield was 85.4% (0.626 g) of 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 fumarate salt. Examination by PLM showed that the batch may contain amorphous content. Acetone with 10% water (12.9 mL) was added to the fumarate salt, and the resulting mixture stirred several hours at room temperature. The product was filtered, washed with acetone with 10% water, and dried overnight in a vacuum oven at 50° C. with a slow nitrogen bleed. The yield was 51.3% (0.376 g) of 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 fumarate salt with a melting onset at 192° C. (determined by DSC).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationThe product was filtered
  3. washwashed with acetone with 5% water
  4. customdried overnight in a vacuum oven at 50° C. with a slow nitrogen

Sources & evidence

ORD record
ord-6caec01667974fc9a57b1d8ae2a907f1
Source dataset
uspto-grants-2010_03
Patent number
US07674789B2

Reaction notes

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