Diisopropylethylamine → [(2R)-3-(2-{2-chloro-5-fluoro-6-[(2S)-2-(3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-1-pyrrolidinyl]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide

HRID 1366714Notes

Reaction equation

HRID 1366714 reaction equation
[CH:1]1([CH2:6][C@@H:7]([C:20]([NH:22][NH:23][C:24]2[C:29]([F:30])=[C:28](Cl)[N:27]=[C:26]([Cl:32])[N:25]=2)=[O:21])[CH2:8][N:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:10]=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:33]1[CH2:37][CH2:36][CH2:35][C@H:34]1[CH2:38][N:39]1[C:43]2[N:44]=[CH:45][N:46]=[CH:47][C:42]=2[N:41]=[N:40]1.CCN(C(C)C)C(C)C>CS(C)=O>[Cl:32][C:26]1[N:25]=[C:24]([NH:23][NH:22][C:20](=[O:21])[C@H:7]([CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[CH2:8][N:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:10]=[O:11])[C:29]([F:30])=[C:28]([N:33]2[CH2:37][CH2:36][CH2:35][C@H:34]2[CH2:38][N:39]2[C:43]3[N:44]=[CH:45][N:46]=[CH:47][C:42]=3[N:41]=[N:40]2)[N:27]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 669365273-[(2S)-2-pyrrolidinylmethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidineHCID 86637038{(2R)-2-(cyclopentylmethyl)-3-[2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)hydrazino]-3-oxopropyl}[(phenylmethyl)oxy]formamide

Product 1

HCID 86637039[(2R)-3-(2-{2-chloro-5-fluoro-6-[(2S)-2-(3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-1-pyrrolidinyl]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamideYield 23.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
65 °C

Procedure

{(2R)-2-(Cyclopentylmethyl)-3-[2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)hydrazino]-3-oxopropyl}[(phenylmethyl)oxy]formamide (136 mg, 0.278 mmol) and 3-[(2S)-2-pyrrolidinylmethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidine (63 mg, 0.308 mmol) were dissolved in DMSO (5 mL), then DIEA (59 μL, 0.308 mmol) was added, and the solution was heated at 65° C. overnight. When the reaction was complete as determined by LCMS, the solution was concentrated in vacuo, and the resulting crude product was purified by RP-HPLC to provide [(2R)-3-(2-{2-chloro-5-fluoro-6-[(2S)-2-(3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-1-pyrrolidinyl]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (43 mg, 21%). LCMS: (M+H)+: 651.6.

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. customthe resulting crude product was purified by RP-HPLC

Sources & evidence

ORD record
ord-b1c6ef3bcf52426ba8b04e20f069c00b
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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