Monomethyl terephthalate → Methyl 4-(1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoate

HRID 1410101Notes

Reaction equation

HRID 1410101 reaction equation
Cl.[NH2:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH3:27])[N:19]=3)[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=2)[CH2:4]1.[CH3:28][O:29][C:30]([C:32]1[CH:40]=[CH:39][C:35]([C:36](O)=[O:37])=[CH:34][CH:33]=1)=[O:31].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([NH:17][C:10]2[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=[C:8]([N:5]3[CH2:6][CH2:7][CH:3]([NH:2][C:36]([C:35]4[CH:39]=[CH:40][C:32]([C:30]([O:29][CH3:28])=[O:31])=[CH:33][CH:34]=4)=[O:37])[CH2:4]3)[N:9]=2)=[N:19][C:20]=1[O:26][CH3:27]

Participants

8

Reactant 5

HCID 15513Monomethyl terephthalateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 683793615-(3-aminopyrrolidin-1-yl)-N-(5,6-dimethoxypyridin-2-yl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride

Product 1

HCID 68379246Methyl 4-(1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoateYield 94.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-(3-aminopyrrolidin-1-yl)-N-(5,6-dimethoxypyridin-2-yl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride (283 mg, 0.69 mmol), 4-(methoxycarbonyl)benzoic acid (161 mg, 0.89 mmol) in 10 mL of DMF were added HATU (340 mg, 0.89 mmol), DIEA (267 mg, 2.07 mmol), EDCI (145 mg, 0.759 mmol) and DMAP (93 mg, 0.76 mmol) at room temperature. Then the reaction mixture was stirred at room temperature for 24 hours. The solvent was evaporated at 80° C. at reduced pressure and the residue was purified by silica gel chromatography (silica gel 200-300 mesh, eluting with a mixture of dichloromethane and methanol (20:1)) to give methyl 4-(1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoate (350 mg, 94%) as a yellow solid. LC-MS: 536.1 [M+H]+, tR=1.68 min.

Workup

  1. customThe solvent was evaporated at 80° C. at reduced pressure
  2. customthe residue was purified by silica gel chromatography (silica gel 200-300 mesh
  3. washeluting with a mixture of dichloromethane and methanol (20:1))

Sources & evidence

ORD record
ord-9045b216506b4750b09dfa348e8c912d
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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