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Methyl 3-mercaptopropionate → Ethyl 3-(5-(benzyloxy)-6-(thiazolo[5,4-b]pyridin-2-ylamino)pyridin-3-ylthio)propanoate

HRID 1426161
Notes
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Reaction equation

HRID 1426161 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH:16][C:17]2[S:18][C:19]3[C:24]([N:25]=2)=[CH:23][CH:22]=[CH:21][N:20]=3)=[N:11][CH:12]=[C:13](Br)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[SH:26][CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30].[CH2:33](N(C(C)C)C(C)C)C.[Cl-].[NH4+]>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.ClCCl.O1CCOCC1>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([S:26][CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:12]=[N:11][C:10]=1[NH:16][C:17]1[S:18][C:19]2[C:24]([N:25]=1)=[CH:23][CH:22]=[CH:21][N:20]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 4

HCID 18050Methyl 3-mercaptopropionateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 16661301N-(3-(Benzyloxy)-5-bromopyridin-2-yl)thiazolo[5,4-b]pyridin-2-amine

Product 1

HCID 86639698Ethyl 3-(5-(benzyloxy)-6-(thiazolo[5,4-b]pyridin-2-ylamino)pyridin-3-ylthio)propanoateYield 110.7%

Reagents, catalysts & solvents

5
HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A 500 mL round-bottomed flask was charged with N-(3-(benzyloxy)-5-bromopyridin-2-yl)thiazolo[5,4-b]pyridin-2-amine (2.00 g, 4.839 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.1400 g, 0.2420 mmol), Pd2dba3 (0.1108 g, 0.1210 mmol), methyl 3-mercaptopropanoate (0.5628 ml, 5.081 mmol), N-ethyl-N-isopropylpropan-2-amine (1.686 ml, 9.678 mmol), and dioxane (125 mL). The reaction mixture was heated at 95° C. under nitrogen for three hours. Saturated ammonium chloride and dichloromethane were added. The reaction mixture was filtered and the solids were washed with water to the title compound (2.425 g, 110.7% yield) containing a small amount of diisopropylethylamine impurity. 1H NMR (DMSO-d6) δ 10.89 (s, 1H), 8.36 (d, 1H), 7.96 (d, 1H), 7.95 (s, 1H), 7.60 (m, 3H), 7.42 (m, 3H), 7.35 (m, 1H), 5.34 (s, 2H), 3.59 (s, 3H), 3.12 (t, 2H), 2.54 (t, 2H). Mass spectrum (apci) m/z=453.1 (M+H).

Workup

  1. filtrationThe reaction mixture was filtered

Sources & evidence

ORD record
ord-46a4db084f984238ba13b8b3eb19eb68
Source dataset
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08933077B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes