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

HRID 1366589Notes

Reaction equation

HRID 1366589 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:20]=[O:21])[O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:22][C:23]1[C:24]([NH:40][NH2:41])=[N:25][C:26]([CH3:39])=[N:27][C:28]=1[N:29]1[CH2:32][C:31]([CH3:38])([N:33]2[CH2:37][CH2:36][CH2:35][CH2:34]2)[CH2:30]1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[CH:1]1([CH2:6][C@@H:7]([C:8]([NH:41][NH:40][C:24]2[C:23]([F:22])=[C:28]([N:29]3[CH2:30][C:31]([CH3:38])([N:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)[CH2:32]3)[N:27]=[C:26]([CH3:39])[N:25]=2)=[O:10])[CH2:11][N:12]([O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[CH:20]=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5]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 669366335-Fluoro-4-hydrazino-2-methyl-6-[3-methyl-3-(1-pyrrolidinyl)-1-azetidinyl]pyrimidine

Product 1

HCID 86636996[(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-methyl-6-[3-methyl-3-(1-pyrrolidinyl)-1-azetidinyl]-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamideYield 58.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid (107 mg, 0.357 mmol), 5-fluoro-4-hydrazino-2-methyl-6-[3-methyl-3-(1-pyrrolidinyl)-1-azetidinyl]pyrimidine (100 mg, 0.357 mmol), EDC (82 mg, 0.428 mmol), HOAt (53 mg, 0.393 mmol), and NMM (0.20 mL, 1.79 mmol) in DMF (5 ml) was stirred at room temperature overnight. The reaction mixture was then purified via RP-HPLC to provide [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-methyl-6-[3-methyl-3-(1-pyrrolidinyl)-1-azetidinyl]-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide (118 mg, 58%). LCMS: (M+H)+: 562.2.

Workup

  1. customThe reaction mixture was then purified via RP-HPLC

Sources & evidence

ORD record
ord-a86a53d719f04825a4c240466803862d
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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