2-Methyl-2-butanol → 2-[4-(1-Hydroxy-1-methylethyl)phenyl]-5-{[6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-2-yl]amino}-1,3-thiazole-4-carboxamide

HRID 2060616Notes

Reaction equation

HRID 2060616 reaction equation
[NH2:1][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([OH:16])([CH3:15])[CH3:14])=[CH:9][CH:8]=2)=[N:4][C:3]=1[C:17]([NH2:19])=[O:18].Br[C:21]1[N:26]=[C:25]([CH:27]([OH:32])[C:28]([F:31])([F:30])[F:29])[CH:24]=[CH:23][CH:22]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[K+].[K+].C(O)(CC)(C)C>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]>[OH:16][C:13]([C:10]1[CH:9]=[CH:8][C:7]([C:5]2[S:6][C:2]([NH:1][C:21]3[CH:22]=[CH:23][CH:24]=[C:25]([CH:27]([OH:32])[C:28]([F:31])([F:30])[F:29])[N:26]=3)=[C:3]([C:17]([NH2:19])=[O:18])[N:4]=2)=[CH:12][CH:11]=1)([CH3:15])[CH3:14]

Participants

7

Reactant 5

HCID 64052-Methyl-2-butanolHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 583352521-(6-Bromopyridin-2-yl)-2,2,2-trifluoroethan-1-olHCID 583352645-Amino-2-[4-(1-hydroxy-1-methylethyl)phenyl]-1,3-thiazole-4-carboxamide

Product 1

HCID 451018712-[4-(1-Hydroxy-1-methylethyl)phenyl]-5-{[6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-2-yl]amino}-1,3-thiazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

The title compound was prepared as described in Example 9, Step 2 using 5-amino-2-[4-(1-hydroxy-1-methylethyl)phenyl]-1,3-thiazole-4-carboxamide (Example 5, Step 3) (150 mg, 0.54 mmol), 1-(6-bromopyridin-2-yl)-2,2,2-trifluoroethanol (138 mg, 0.54 mmol), Pd2(dba)3 (30 mg, 0.032 mmol), X-PHOS (77 mg, 0.16 mmol), potassium carbonate (82 mg, 0.60 mmol), and tert-amyl alcohol (1.2 ml) as starting materials. 1H NMR (600 MHz, d6-DMSO) δ 11.33 (s, 1H), 7.85 (d, 2H), 7.80 (t, 1H), 7.73 (s, 1H), 7.62 (s, 1H), 7.55 (d, 2H), 7.21 (d, 1H), 7.19 (d, 1H), 7.02 (d, 1H), 5.19 (m, 1H), 5.08 (s, 1H), 1.42 (s, 6H). LRMS (APCI) calc'd for C20H20F3N4O3S [M+H]+ 453.1, found 453.0.

Sources & evidence

ORD record
ord-2abd752b86844945b576a89ccd772476
Source dataset
uspto-grants-2012_10
Patent number
US08278335B2

Reaction notes

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