1,2-Dichloroethane → 3-Fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)benzonitrile

HRID 1177460Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[S:12][C:13]2[C:18]([N:19]=1)=[CH:17][CH:16]=[C:15]([C:20]1([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:22][CH2:21]1)[N:14]=2)[C:5](O)=O.ClCCCl.C(#[N:35])C.ClS(N=C=O)(=O)=O.C(N(CC)CC)C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[S:12][C:13]2[C:18]([N:19]=1)=[CH:17][CH:16]=[C:15]([C:20]1([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:22][CH2:21]1)[N:14]=2)[C:5]#[N:35]

Participants

Conditions

Temperature: 90 °C

Procedure

To a stirred solution of 3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)benzoic acid (0.222 g, 0.569 mmol) in 1,2-dichloroethane (1.5 mL, 19 mmol) and acetonitrile (1.5 mL, 29 mmol) under argon were added chlorosulfonyl isocyanate (0.074 mL, 0.853 mmol) and triethylamine (0.12 mL, 0.853 mmol). The reaction mixture was stirred at 90° C. for 18 h. The cooled reaction mixture was diluted with CH2Cl2 and washed with saturated aqueous NaHCO3 solution and brine; dried (MgSO4). ISCO purification (with 10% to 50% EtOAc/hexanes) afforded 3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)benzonitrile as an off-white solid. MS (ESI) m/z: Calculated: 371.1; Observed: 372.0 (M++1).

Workup

customThe cooled reaction mixture
washwashed with saturated aqueous NaHCO3 solution and brine
dry with materialdried (MgSO4)
customISCO purification (with 10% to 50% EtOAc/hexanes)

Sources & evidence

ORD record: ord-139c1529a3154b2c9aac69618133f48f
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842685B2

Reaction notes

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