tert-Butylimino-tri(pyrrolidino)phosphorane → HCID 86698055, compound

HRID 518902Notes

Reaction equation

HRID 518902 reaction equation
CC(N=P(N1CCCC1)(N1CCCC1)N1CCCC1)(C)C.[CH3:22][O:23][C:24]1[C:29]([C:30]2[C:34]3[N:35]=[C:36](S(C)(=O)=O)[N:37]=[CH:38][C:33]=3[S:32][C:31]=2[C:43]([O:45][CH3:46])=[O:44])=[CH:28][CH:27]=[C:26]([CH3:47])[N:25]=1.[CH3:48][C:49]1[C:50]([N:62]2[CH2:67][CH2:66][N:65]([CH3:68])[CH2:64][CH2:63]2)=[CH:51][C:52]([O:58][CH:59]([CH3:61])[CH3:60])=[C:53]([NH:55][CH:56]=[O:57])[CH:54]=1>CN(C=O)C>[CH:56]([N:55]([C:53]1[CH:54]=[C:49]([CH3:48])[C:50]([N:62]2[CH2:63][CH2:64][N:65]([CH3:68])[CH2:66][CH2:67]2)=[CH:51][C:52]=1[O:58][CH:59]([CH3:61])[CH3:60])[C:36]1[N:37]=[CH:38][C:33]2[S:32][C:31]([C:43]([O:45][CH3:46])=[O:44])=[C:30]([C:29]3[C:24]([O:23][CH3:22])=[N:25][C:26]([CH3:47])=[CH:27][CH:28]=3)[C:34]=2[N:35]=1)=[O:57]

Participants

5

Reactant 3

HCID 3856267tert-Butylimino-tri(pyrrolidino)phosphoraneHCID 86698056HCID 86698056, compoundHCID 86698057HCID 86698057, compound

Product 1

HCID 86698055HCID 86698055, compoundYield 91.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.7 ml of 1-[N-(2-methylpropan-2-yl)-P,P-di(pyrrolidin-1-yl)phosphorimidoyl]pyrrolidine (BTPP) is added to a mixture of 300 mg of methyl 7-(2-methoxy-6-methylpyridin-3-yl)-2-(methylsulfonyl)thieno[3,2-d]pyrimidine-6-carboxylate and 231 mg of N-[5-methyl-4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]formamide in 8 ml of anhydrous DMF. The mixture is stirred at ambient temperature for 16 h, and then evaporated under vacuum at a temperature of 55° C., and the residue is diluted with ethyl acetate and water. The aqueous phase is extracted three times with ethyl acetate. The organic phases are washed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under vacuum. The crude product is purified on 25 g of silica, elution being carried out with 50-100% of acetone in dichloromethane so as to obtain 422 mg of methyl 2-{formyl[5-methyl-4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]amino}-7-(2-methoxy-6-methylpyridin-3-yl)thieno[3,2-d]pyrimidine-6-carboxylate in the form of an orangey-coloured solid.

Workup

  1. customevaporated under vacuum at a temperature of 55° C.
  2. additionthe residue is diluted with ethyl acetate and water
  3. extractionThe aqueous phase is extracted three times with ethyl acetate
  4. washThe organic phases are washed with a saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe crude product is purified on 25 g of silica, elution

Sources & evidence

ORD record
ord-c8b5c02dfa4c49808194752e52abe4d3
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

Loading…