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

HRID 1426161Notes

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

Participants

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

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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