tert-Butylimino-tri(pyrrolidino)phosphorane → Methyl 2-{formyl[4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]amino}-7-(2-methoxyphenyl)thieno[3,2-d]pyrimidine-6-carboxylate

HRID 518901Notes

Reaction equation

HRID 518901 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:13]2[N:14]=[C:15](S(C)(=O)=O)[N:16]=[CH:17][C:12]=2[S:11][C:10]=1[C:22]([O:24][CH3:25])=[O:23].[CH3:26][N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[CH:37][C:36]([NH:39][CH:40]=[O:41])=[C:35]([O:42][CH:43]([CH3:45])[CH3:44])[CH:34]=2)[CH2:29][CH2:28]1.CC(N=P(N1CCCC1)(N1CCCC1)N1CCCC1)(C)C>CN(C=O)C>[CH:40]([N:39]([C:36]1[CH:37]=[CH:38][C:33]([N:30]2[CH2:29][CH2:28][N:27]([CH3:26])[CH2:32][CH2:31]2)=[CH:34][C:35]=1[O:42][CH:43]([CH3:45])[CH3:44])[C:15]1[N:16]=[CH:17][C:12]2[S:11][C:10]([C:22]([O:24][CH3:25])=[O:23])=[C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[O:2][CH3:1])[C:13]=2[N:14]=1)=[O:41]

Participants

5

Reactant 3

HCID 3856267tert-Butylimino-tri(pyrrolidino)phosphoraneHCID 86698041Methyl 7-(2-methoxyphenyl)-2-(methylsulfonyl)thieno[3,2-d]pyrimidine-6-carboxylateHCID 86698043N-[4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]formamide

Product 1

HCID 86698054Methyl 2-{formyl[4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]amino}-7-(2-methoxyphenyl)thieno[3,2-d]pyrimidine-6-carboxylateYield 82.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1.80 g of methyl 7-(2-methoxyphenyl)-2-(methylsulfonyl)thieno[3,2-d]pyrimidine-6-carboxylate, 1.37 g of N-[4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]formamide and 4.44 g of 1-[N-(2-methylpropan-2-yl)-P,P-di(pyrrolidin-1-yl)phosphorimidoyl]pyrrolidine (BTPP) in 50 ml of anhydrous DMF is stirred at ambient temperature for 16 h. The mixture is 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 100 g of silica, elution being carried out with 0-2.5% of methanol containing 10% by volume of 28% aqueous ammonia solution in dichloromethane, so as to obtain 2.264 g of methyl 2-{formyl[4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]amino}-7-(2-methoxyphenyl)thieno[3,2-d]pyrimidine-6-carboxylate in the form of a brown solid.

Workup

  1. customThe mixture is then evaporated 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 100 g of silica, elution

Sources & evidence

ORD record
ord-20182967b02740f5858b0738c0bca3e7
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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