2,6-Lutidine → (3R*,5S*)-5-(6-Chloro-pyrimidin-4-ylamino)-piperidine-3-carboxylic acid cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-amide

HRID 1698365Notes

Reaction equation

HRID 1698365 reaction equation
C(OC([N:8]1[CH2:13][C@H:12]([C:14](=[O:34])[N:15]([CH:31]2[CH2:33][CH2:32]2)[CH2:16][C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[CH:18]=2)[CH2:11][C@H:10]([NH2:35])[CH2:9]1)=O)(C)(C)C.Cl[C:37]1[CH:42]=[C:41]([Cl:43])[N:40]=[CH:39][N:38]=1.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.N1C(C)=CC=CC=1C>CC#N>[CH:31]1([N:15]([CH2:16][C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[CH:18]=2)[C:14]([C@@H:12]2[CH2:11][C@H:10]([NH:35][C:37]3[CH:42]=[C:41]([Cl:43])[N:40]=[CH:39][N:38]=3)[CH2:9][NH:8][CH2:13]2)=[O:34])[CH2:32][CH2:33]1

Participants

6

Reactant 4

HCID 79372,6-LutidineHCID 65367Trimethylsilyl triflateHCID 709434,6-DichloropyrimidineHCID 69071766(3S*,5R*)-3-Amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 57870341(3R*,5S*)-5-(6-Chloro-pyrimidin-4-ylamino)-piperidine-3-carboxylic acid cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-amide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Procedure

The title compound is prepared analogously as described in Example 154 using (3S*,5R*)-3-Amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid tert-butyl ester and 4,6-dichloropyrimidine followed by deprotection of Boc using TMSOTf and 2,6-lutidine. MS: 497 (Cl35) [M+H]+; tR (HPLC, ACQUITY UPLC™ BEH C18 1.7 μm, 50×2.1 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 1.5 min, flow 0.5 ml/min): 2.77 min.

Workup

  1. custom2.77 min.

Sources & evidence

ORD record
ord-269c9611177449e49c5f2d713840c7fa
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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