2-Methyl-2-butanol → 2-[2,6-Difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-{[5-(1-hydroxy-1-methylethyl)-6-methylpyridin-2-yl]amino}-1,3-thiazole-4-carboxamide

HRID 2060626Notes

Reaction equation

HRID 2060626 reaction equation
[NH2:1][C:2]1[S:6][C:5]([C:7]2[C:12]([F:13])=[CH:11][C:10]([C:14]([OH:17])([CH3:16])[CH3:15])=[CH:9][C:8]=2[F:18])=[N:4][C:3]=1[C:19]([NH2:21])=[O:20].Cl[C:23]1[N:28]=[C:27]([CH3:29])[C:26]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:25][CH:24]=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]>[F:13][C:12]1[CH:11]=[C:10]([C:14]([OH:17])([CH3:16])[CH3:15])[CH:9]=[C:8]([F:18])[C:7]=1[C:5]1[S:6][C:2]([NH:1][C:23]2[CH:24]=[CH:25][C:26]([C:30]([OH:33])([CH3:31])[CH3:32])=[C:27]([CH3:29])[N:28]=2)=[C:3]([C:19]([NH2:21])=[O:20])[N:4]=1

Participants

7

Reactant 5

HCID 64052-Methyl-2-butanolHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 583352662-(6-Chloro-2-methylpyridin-3-yl)propan-2-olHCID 583352715-Amino-2-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-1,3-thiazole-4-carboxamide

Product 1

HCID 446231032-[2,6-Difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-{[5-(1-hydroxy-1-methylethyl)-6-methylpyridin-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 15, Step 7 using 5-amino-2-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-1,3-thiazole-4-carboxamide (Example 15, Step 5) (150 mg, 0.48 mmol), 2-(6-chloro-2-methylpyridin-3-yl)propan-2-ol (Example 13, Step 1) (89 mg, 0.48 mmol), Pd2(dba)3 (44 mg, 0.048 mmol), X-PHOS (114 mg, 0.24 mmol), potassium carbonate (66 mg, 0.48 mmol), and tert-amyl alcohol (0.96 ml) as starting materials. 1H NMR (500 MHz, d6-DMSO) δ 11.23 (s, 1H), 7.75 (d, 1H), 7.62 (s, 1H), 7.47 (s, 1H), 7.32 (d, 2H), 7.00 (d, 1H), 5.37 (s, 1H), 5.02 (s, 1H), 2.69 (s, 3H), 1.49 (s, 6H), 1.44 (s, 6H). LRMS (APCI) calc'd for C22H25F2N4O3S [M+H]+ 463.2, found 463.0.

Sources & evidence

ORD record
ord-d74f06890763413d914bf7da862b8c9a
Source dataset
uspto-grants-2012_10
Patent number
US08278335B2

Reaction notes

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