1,2-Dichloroethane → [(2R)-2-(Cyclopentyl methyl)-3-(2-{5-fluoro-2-methyl-6-[(1,3-thiazol-2-ylmethyl)amino]-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide

HRID 1366469Notes

Reaction equation

HRID 1366469 reaction equation
[F:1][C:2]1[C:3]([NH:16][NH2:17])=[N:4][C:5]([CH3:15])=[N:6][C:7]=1[NH:8][CH2:9][C:10]1[S:11][CH:12]=[CH:13][N:14]=1.[CH:18]1([CH2:23][C@H:24]([CH2:28][N:29]([CH:37]=[O:38])[O:30][CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)[C:25](O)=[O:26])[CH2:22][CH2:21][CH2:20][CH2:19]1.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CN(C=O)C>[CH:18]1([CH2:23][C@@H:24]([C:25]([NH:17][NH:16][C:3]2[C:2]([F:1])=[C:7]([NH:8][CH2:9][C:10]3[S:11][CH:12]=[CH:13][N:14]=3)[N:6]=[C:5]([CH3:15])[N:4]=2)=[O:26])[CH2:28][N:29]([O:30][CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)[CH:37]=[O:38])[CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 57937086(2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acidHCID 669358995-Fluoro-4-hydrazino-2-methyl-6-[(1,3-thiazol-2-ylmethyl)amino]pyrimidine

Product 1

HCID 86636949[(2R)-2-(Cyclopentyl methyl)-3-(2-{5-fluoro-2-methyl-6-[(1,3-thiazol-2-ylmethyl)amino]-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamideYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Fluoro-4-hydrazino-2-methyl-6-[(1,3-thiazol-2-ylmethyl)amino]pyrimidine (80 mg, 0.33 mmol), (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid (Hunigs base salt, 140 mg, 0.33 mmol), and HOAt (45 mg, 0.33 mmol) were dissolved in 3 mL of DMF. NMM (0.1 mL, 0.9 mmol) was added, followed by EDC (65 mg, 0.33 mmol). After stirring overnight at room temperature, the reaction mixture was purified by RP-HPLC to provide [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-methyl-6-[(1,3-thiazol-2-ylmethyl)amino]-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide (72 mg, 45%). LCMS: (M+H)+: 536.2.

Workup

  1. customthe reaction mixture was purified by RP-HPLC

Sources & evidence

ORD record
ord-bcdd8ab0691a42d7ad6d998f755e7edd
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

Loading…