1-Pyrrolidineethanamine → 5-methyl-N-(2-(pyrrolidin-1-yl)ethyl)-4-(2-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-ylamino)thieno[2,3-d]pyrimidine-6-carboxamide

HRID 450559Notes

Reaction equation

HRID 450559 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]1[C:34]2[C:33]([NH:35][C:36]3[C:37]([O:42][CH:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)=[N:38][CH:39]=[CH:40][CH:41]=3)=[N:32][CH:31]=[N:30][C:29]=2[S:28][C:27]=1[C:49](O)=[O:50].CCN(C(C)C)C(C)C.[NH2:61][CH2:62][CH2:63][N:64]1[CH2:68][CH2:67][CH2:66][CH2:65]1>CN(C=O)C>[CH3:25][C:26]1[C:34]2[C:33]([NH:35][C:36]3[C:37]([O:42][CH:43]4[CH2:44][CH2:45][O:46][CH2:47][CH2:48]4)=[N:38][CH:39]=[CH:40][CH:41]=3)=[N:32][CH:31]=[N:30][C:29]=2[S:28][C:27]=1[C:49]([NH:61][CH2:62][CH2:63][N:64]1[CH2:68][CH2:67][CH2:66][CH2:65]1)=[O:50]

Participants

6

Reactant 4

HCID 13441-PyrrolidineethanamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 584131025-methyl-4-(2-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-ylamino)thieno[2,3-d]pyrimidine-6-carboxylic acid

Product 1

HCID 461821285-methyl-N-(2-(pyrrolidin-1-yl)ethyl)-4-(2-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-ylamino)thieno[2,3-d]pyrimidine-6-carboxamideYield 42.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

HATU (0.105 g, 0.28 mmol) was added into a mixture of 5-methyl-4-(2-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-ylamino)thieno[2,3-d]pyrimidine-6-carboxylic acid (0.097 g, 0.25 mmol) and Hünig's base (44 μL, 0.25 mmol) in DMF (2.0 mL) at 0° C. The reaction mixture was stirred at 0° C. for 0.5 hours. 1-(2-Aminoethyl)-pyrrolidine (157 μL, 1.25 mmol) was added and the coolant removed. The reaction mixture was stirred at ambient temperature overnight. The solvent was concentrated in vacuo, the crude material added into water (10 mL) and the aqueous layer extracted into DCM. The product was purified by flash-column chromatography (DCM→10% ammonia/MeOH/DCM) to yield the title compound as off-white solid (0.051 g, 42% yield).

Workup

  1. customthe coolant removed
  2. stirringThe reaction mixture was stirred at ambient temperature overnight
  3. concentrationThe solvent was concentrated in vacuo
  4. additionthe crude material added into water (10 mL)
  5. extractionthe aqueous layer extracted into DCM
  6. customThe product was purified by flash-column chromatography (DCM→10% ammonia/MeOH/DCM)

Sources & evidence

ORD record
ord-5e4a914bd518453fa71c34352c6f5203
Source dataset
uspto-grants-2013_07
Patent number
US08486953B2

Reaction notes

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