Diisopropylethylamine → (4-Methylpiperazin-1-yl)-[3-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-ylamino)phenyl]methanone

HRID 1805989Notes

Reaction equation

HRID 1805989 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=2)[C:15]([OH:17])=O)[C:5]2[S:10][CH2:9][CH2:8][C:6]=2[N:7]=1.CN(C(ON1N=[N:36][C:31]2C=[CH:33][CH:34]=[N:35][C:30]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:45](N(C(C)C)CC)(C)C.ClC1N=C(CCCN)C2S(=O)(=O)CCC=2N=1>CS(C)=O>[CH3:45][N:35]1[CH2:30][CH2:31][N:36]([C:15]([C:14]2[CH:18]=[CH:19][CH:20]=[C:12]([NH:11][C:4]3[C:5]4[S:10][CH2:9][CH2:8][C:6]=4[N:7]=[C:2]([Cl:1])[N:3]=3)[CH:13]=2)=[O:17])[CH2:33][CH2:34]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 576001073-(2-Chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-ylamino)benzoic acidHCID 86616274(2-chloro-5,5-dioxo-6,7-dihydro-5H-5lambda6-thieno[3,2-d]pyrimidin-4-yl)propylamine

Product 1

HCID 86616277(4-Methylpiperazin-1-yl)-[3-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-ylamino)phenyl]methanoneYield 33%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

0.600 g (1.95 mmol) of 3-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-ylamino)benzoic acid (I), 0.741 g (1.95 mmol) of O-(7-azabenzotriazol-1-yl-)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU), and 0.680 mL (3.90 mmol) of is diisopropylethylamine are placed in 10 mL of dimethylsulfoxide, then stirred for 0.5 hours at ambient temperature. 0.220 mL (1.95 mmol) of methylpiperazine (II) is added, then the mixture is stirred for 3 hours at ambient temperature. Then the reaction mixture is concentrated by evaporation and the residue is combined with water. Any precipitate formed is suction filtered and dried. The crude product is purified by chromatography through a 50 g silica cartridge with ethyl acetate/methanol 8:2. 0.250 g of product III (33%) is obtained.

Workup

  1. stirringthe mixture is stirred for 3 hours at ambient temperature
  2. concentrationThen the reaction mixture is concentrated by evaporation
  3. customAny precipitate formed
  4. filtrationfiltered
  5. customdried
  6. customThe crude product is purified by chromatography through a 50 g silica cartridge with ethyl acetate/methanol 8:2

Sources & evidence

ORD record
ord-576ddd9f4f8845ffb8b3373a93bf99fd
Source dataset
uspto-grants-2013_01
Patent number
US08354531B2

Reaction notes

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