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

HRID 2060644Notes

Reaction equation

HRID 2060644 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][C:8]=2[F:17])=[N:4][C:3]=1[C:18]([NH2:20])=[O:19].Br[C:22]1[N:27]=[C:26]([CH:28]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[CH2:29][OH:30])[CH:25]=[CH:24][CH:23]=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:17][C:8]1[CH:9]=[C:10]([C:13]([OH:16])([CH3:15])[CH3:14])[CH:11]=[CH:12][C:7]=1[C:5]1[S:6][C:2]([NH:1][C:22]2[CH:23]=[CH:24][CH:25]=[C:26]([CH:28]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH2:29][OH:30])[N:27]=2)=[C:3]([C:18]([NH2:20])=[O:19])[N:4]=1

Participants

7

Reactant 5

HCID 64052-Methyl-2-butanolHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 583352575-Amino-2-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-1,3-thiazole-4-carboxamideHCID 583352752-(6-Bromopyridin-2-yl)-2-morpholin-4-ylethanol

Product 1

HCID 451019992-[2-Fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-{[6-(2-hydroxy-1-morpholin-4-ylethyl)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 1, Step 2 using 5-amino-2-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-1,3-thiazole-4-carboxamide (115 mg, 0.39 mmol), 2-(6-bromopyridin-2-yl)-2-morpholin-4-ylethanol (Enantiomer B) (Example 3, Step 1, chiral separation) (112 mg, 0.39 mmol), Pd2(dba)3 (36 mg, 0.039 mmol), X-PHOS (93 mg, 0.20 mmol), potassium carbonate (54 mg, 0.39 mmol), and tert-amyl alcohol (0.8 ml) as starting materials. 1H NMR (500 MHz, d6-DMSO) δ 11.25 (s, 1H), 8.29 (t, 1H), 7.86 (s, 1H), 7.70 (m, III), 7.65 (s, 1H), 7.42 (m, 2H), 7.10 (d, 1H), 6.92 (d, 1H), 5.24 (s, 1H), 4.47 (t, 1H), 4.00 (m, 2H), 3.65 (t, 1H), 3.54 (m, 4H), 2.51 (m, 4H), 1.44 (s, 6H). LRMS (APCI) calc'd for C24H29FN5O4S [M+H]+ 502.2, found 502.0.

Sources & evidence

ORD record
ord-5b27c70670be4a4dafc48505d1000a81
Source dataset
uspto-grants-2012_10
Patent number
US08278335B2

Reaction notes

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