Phosphoric Acid → 1226999-07-0

HRID 1186634Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([NH:31][C:32]([C:34]2([C:37]([NH:39][C:40]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=3)=[O:38])[CH2:36][CH2:35]2)=[O:33])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1.[P:47](=[O:51])([OH:50])([OH:49])[OH:48]>CC(C)=O.O>[P:47]([OH:51])([OH:50])([OH:49])=[O:48].[P:47]([OH:51])([OH:50])([OH:49])=[O:48].[F:1][C:2]1[CH:3]=[C:4]([NH:31][C:32]([C:34]2([C:37]([NH:39][C:40]3[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=3)=[O:38])[CH2:36][CH2:35]2)=[O:33])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 22.5 °C

Procedure

N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide free base was dissolved in acetone (46.0 L) and water (12.0 L). Phosphoric acid (85%, 1.2 L) was added at a rate such that the batch temperature did not exceed 30° C. The batch was maintained at approximately 15-30° C. with stirring for 1 h during which time the product precipitated. The solids were collected by filtration, washed with acetone and dried at approximately 60° C. under vacuum to afford N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide bisphosphate (5.5 kg).

Workup

customdid not exceed 30° C
customprecipitated
filtrationThe solids were collected by filtration
washwashed with acetone
customdried at approximately 60° C. under vacuum

Sources & evidence

ORD record: ord-1955c45068ba4525a8ab37ad6845f7f2
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673912B2

Reaction notes

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