Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 2-(4-chlorophenyl)-1-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-(2-methylaziridin-1-yl)propan-1-one

HRID 625082Notes

Reaction equation

HRID 625082 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[CH3:27][C@H:28]1[C:36]2[C:35]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[N:34][CH:33]=[N:32][C:31]=2[CH2:30][S:29]1.[Cl:43][C:44]1[CH:49]=[CH:48][C:47]([CH:50]([CH2:54][N:55]2[CH2:57][CH:56]2[CH3:58])[C:51](O)=[O:52])=[CH:46][CH:45]=1>C(Cl)Cl>[Cl:43][C:44]1[CH:49]=[CH:48][C:47]([CH:50]([CH2:54][N:55]2[CH2:57][CH:56]2[CH3:58])[C:51]([N:40]2[CH2:41][CH2:42][N:37]([C:35]3[C:36]4[C@H:28]([CH3:27])[S:29][CH2:30][C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:38][CH2:39]2)=[O:52])=[CH:46][CH:45]=1

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67459940HCID 67459940, compoundHCID 866753362-(4-Chlorophenyl)-3-(2-methylaziridin-1-yl)propanoic acid

Product 1

HCID 249507462-(4-chlorophenyl)-1-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-(2-methylaziridin-1-yl)propan-1-oneYield 2.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

HBTU (37 mg, 0.097 mmol) was added to a solution of the (S)-5-methyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (30 mg, 0.097 mmol) and 2-(4-chlorophenyl)-3-(2-methylaziridin-1-yl)propanoic acid (47 mg, 0.097 mmol) in DCM (5 mL) and TEA (1 mL). The mixture was stirred at room temperature for 1 hour. The solvent was removed, and the residue was subject to column chromatography, eluting with EA-DCM/MeOH (20:1-10:1). The product was treated with HCl (4M, 2 mL) afforded 2-(4-chlorophenyl)-1-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-(2-methylaziridin-1-yl)propan-1-one as the HCl salt (1 mg, 2%). LC/MS (APCI+) m/z 458.1.

Workup

  1. customThe solvent was removed
  2. washeluting with EA-DCM/MeOH (20:1-10:1)
  3. additionThe product was treated with HCl (4M, 2 mL)

Sources & evidence

ORD record
ord-195b91389ce74534b141a4f2cc418a02
Source dataset
uspto-grants-2016_04
Patent number
US09303040B2

Reaction notes

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