N,N-Dimethyl-1,3-propanediamine → N-(3-(Dimethylamino)propyl)-4-(4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenyl-amino)thieno[2,3-d]pyrimidine-6-carboxamide mono formate salt

HRID 450550Notes

Reaction equation

HRID 450550 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]2[C:34]3[CH:41]=[C:40]([C:42]([OH:44])=[O:43])[S:39][C:35]=3[N:36]=[CH:37][N:38]=2)=[C:28]([O:45][CH:46]2[CH2:51][CH2:50][O:49][CH2:48][CH2:47]2)[CH:27]=1.CCN(C(C)C)C(C)C.[CH3:61][N:62]([CH3:67])[CH2:63][CH2:64][CH2:65][NH2:66]>CN(C=O)C>[CH:42]([OH:44])=[O:43].[CH3:61][N:62]([CH3:67])[CH2:63][CH2:64][CH2:65][NH:66][C:42]([C:40]1[S:39][C:35]2[N:36]=[CH:37][N:38]=[C:33]([NH:32][C:29]3[CH:30]=[CH:31][C:26]([F:25])=[CH:27][C:28]=3[O:45][CH:46]3[CH2:47][CH2:48][O:49][CH2:50][CH2:51]3)[C:34]=2[CH:41]=1)=[O:43]

Participants

6

Reactant 4

HCID 7993N,N-Dimethyl-1,3-propanediamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 461820834-(4-Fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)thieno[2,3-d]pyrimidine-6-carboxylic acid

Product 1

HCID 46182172N-(3-(Dimethylamino)propyl)-4-(4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenyl-amino)thieno[2,3-d]pyrimidine-6-carboxamide mono formate saltYield 20.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.054 g, 0.14 mmol) was added into a solution of 4-(4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)thieno[2,3-d]pyrimidine-6-carboxylic acid (0.050 g, 0.13 mmol) and Hünig's base (22 μL, 0.13 mmol) in anhydrous DMF (1.0 mL) at 0° C. After 0.5 hours, 3-dimethylamino-1-propylamine (71 μL, 0.64 mmol) was added and the solution allowed to warm to ambient temperature over night. The reaction was concentrated in vacuo and the residue redissolved in dimethyl sulfoxide. The sample was purified by reverse phase preparative HPLC to yield off-white solid (0.007 g, 11%) as the mono-formate salt.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe residue redissolved in dimethyl sulfoxide
  3. customThe sample was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-739df0d75a034095bc2487acb16af76c
Source dataset
uspto-grants-2013_07
Patent number
US08486953B2

Reaction notes

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