tert-Butylimino-tri(pyrrolidino)phosphorane → Methyl 2-{formyl[4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]amino}-7-(5-fluoro-2-methoxyphenyl)thieno[3,2-d]pyrimidine-6-carboxylate

HRID 518904Notes

Reaction equation

HRID 518904 reaction equation
CC(N=P(N1CCCC1)(N1CCCC1)N1CCCC1)(C)C.[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:34]=[CH:33][C:32]([NH:35][CH:36]=[O:37])=[C:31]([O:38][CH:39]([CH3:41])[CH3:40])[CH:30]=2)[CH2:25][CH2:24]1.[F:42][C:43]1[CH:44]=[CH:45][C:46]([O:66][CH3:67])=[C:47]([C:49]2[C:53]3[N:54]=[C:55](S(C)(=O)=O)[N:56]=[CH:57][C:52]=3[S:51][C:50]=2[C:62]([O:64][CH3:65])=[O:63])[CH:48]=1>CN(C=O)C>[CH:36]([N:35]([C:32]1[CH:33]=[CH:34][C:29]([N:26]2[CH2:25][CH2:24][N:23]([CH3:22])[CH2:28][CH2:27]2)=[CH:30][C:31]=1[O:38][CH:39]([CH3:41])[CH3:40])[C:55]1[N:56]=[CH:57][C:52]2[S:51][C:50]([C:62]([O:64][CH3:65])=[O:63])=[C:49]([C:47]3[CH:48]=[C:43]([F:42])[CH:44]=[CH:45][C:46]=3[O:66][CH3:67])[C:53]=2[N:54]=1)=[O:37]

Participants

5

Reactant 3

HCID 3856267tert-Butylimino-tri(pyrrolidino)phosphoraneHCID 86698043N-[4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]formamideHCID 86698061Methyl 7-(5-fluoro-2-methoxyphenyl)-2-(methylsulfonyl)thieno[3,2-d]pyrimidine-6-carboxylate

Product 1

HCID 86698060Methyl 2-{formyl[4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]amino}-7-(5-fluoro-2-methoxyphenyl)thieno[3,2-d]pyrimidine-6-carboxylateYield 96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

0.7 ml of 1-[N-(2-methylpropan-2-yl)-P,P-di(pyrrolidin-1-yl)phosphorimidoyl]pyrrolidine (BTPP) is added to a solution of 245 mg of N-[4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]formamide in 5 ml of anhydrous DMF. After 10 min, a solution of 350 mg of methyl 7-(5-fluoro-2-methoxyphenyl)-2-(methylsulfonyl)thieno[3,2-d]pyrimidine-6-carboxylate in 6.5 ml of anhydrous DMF is added and the mixture is stirred at ambient temperature for 42 h. The mixture is then evaporated under vacuum at a temperature of 60° C., and the residue is purified on 120 g of silica, elution being carried out with 5% of methanol in dichloromethane, so as to obtain 503 mg of methyl 2-{formyl[4-(4-methylpiperazin-1-yl)-2-(propan-2-yloxy)phenyl]amino}-7-(5-fluoro-2-methoxyphenyl)thieno[3,2-d]pyrimidine-6-carboxylate in the form of an orangey-coloured solid.

Workup

  1. customThe mixture is then evaporated under vacuum at a temperature of 60° C.
  2. customthe residue is purified on 120 g of silica, elution

Sources & evidence

ORD record
ord-d67bea04b7624516a1c78d482ce821c0
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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