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

HRID 1366491Notes

Reaction equation

HRID 1366491 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][NH:8][C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([NH:16][NH2:17])[C:10]=2[F:18])[N:6]=1.[CH:19]1([CH2:24][C@H:25]([CH2:29][N:30]([CH:38]=[O:39])[O:31][CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][O:33]2)[C:26](O)=[O:27])[CH2:23][CH2:22][CH2:21][CH2:20]1.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CN(C=O)C>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][NH:8][C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([NH:16][NH:17][C:26](=[O:27])[C@H:25]([CH2:24][CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23]3)[CH2:29][N:30]([O:31][CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[CH:38]=[O:39])[C:10]=2[F:18])[N:6]=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 866369606-{[(2-Amino-1,3-thiazol-4-yl)methyl]amino}-5-fluoro-4-hydrazino-2-methylpyrimidine

Product 1

HCID 86636961[(2R)-3-[2-(6-{[(2-amino-1,3-thiazol-4-yl)methyl]amino}-5-fluoro-2-methyl-4-pyrimidinyl)hydrazino]-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamideYield 47.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-{[(2-Amino-1,3-thiazol-4-yl)methyl]amino}-5-fluoro-4-hydrazino-2-methylpyrimidine (125 mg, 0.44 mmol), (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid (130 mg, 0.44 mmol), and HOAt (65 mg, 0.48 mmol) were dissolved in 4 mL of DMF. NMM (0.15 mL, 1.32 mmol) was added, followed by EDC (96 mg, 0.48 mmol). After stirring overnight at room temperature, the reaction mixture was purified by RP-HPLC to provide [(2R)-3-[2-(6-{[(2-amino-1,3-thiazol-4-yl)methyl]amino}-5-fluoro-2-methyl-4-pyrimidinyl)hydrazino]-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide (114 mg, 46%). LCMS: (M+H)+: 565.3.

Workup

  1. customthe reaction mixture was purified by RP-HPLC

Sources & evidence

ORD record
ord-73ec69c271df46e0a0bf536c0b676f9e
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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