Potassium Carbonate → (2S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(4-(1-methyl-1H-indazol-5-yl)-2-oxopyrrolidin-1-yl)benzo[d]thiazol-6-yl)acetate

HRID 879331Notes

Reaction equation

HRID 879331 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:25]([CH3:26])=[CH:24][C:14]2[N:15]=[C:16]([N:18]3[CH2:22][CH:21]=[CH:20][C:19]3=[O:23])[S:17][C:13]=2[C:12]=1[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:34][N:35]1[C:43]2[C:38](=[CH:39][C:40](B(O)O)=[CH:41][CH:42]=2)[CH:37]=[N:36]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1CC=CCCC=C1.C1CC=CCCC=C1.[Cl-].[Cl-].[Rh].[Rh]>[C:1]([O:5][C@@H:6]([C:11]1[C:25]([CH3:26])=[CH:24][C:14]2[N:15]=[C:16]([N:18]3[CH2:22][CH:21]([C:40]4[CH:39]=[C:38]5[C:43](=[CH:42][CH:41]=4)[N:35]([CH3:34])[N:36]=[CH:37]5)[CH2:20][C:19]3=[O:23])[S:17][C:13]=2[C:12]=1[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 225589101-Methyl-1H-indazole-5-boronic acidHCID 86699848(S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-oxo-2,5-dihydro-1H-pyrrol-1-yl)benzo[d]thiazol-6-yl)acetate

Product 1

HCID 86699849(2S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(4-(1-methyl-1H-indazol-5-yl)-2-oxopyrrolidin-1-yl)benzo[d]thiazol-6-yl)acetate

Reagents, catalysts & solvents 2

HCID 6436379Rhodium, di-mu-chlorobis((1,2,5,6-eta)-1,5-cyclooctadiene)di-CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-oxo-2,5-dihydro-1H-pyrrol-1-yl)benzo[d]thiazol-6-yl)acetate (12 mg, 0.025 mmol) in 1,4-dioxane/water (0.5 mL/50 μL) was added 1-methyl-1H-indazol-5-ylboronic acid (8 mg, 0.050 mmol), followed by chloro(1,5-cyclooctadiene)rhodium (I) dimer (1 mg), BINAP (5 mg), and potassium carbonate solution (2 N, 6 μL). The mixture was purged with nitrogen and heated at 80° C. for 24 hours. The mixture was diluted with EtOAc, and was washed with water and brine, dried with sodium sulfate and filtered. Concentration and purification by flash column chromatography (hexanes/EtOAc) gave (2S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(4-(1-methyl-1H-indazol-5-yl)-2-oxopyrrolidin-1-yl)benzo[d]thiazol-6-yl)acetate. LCMS-ESI+: calc'd for C33H33ClN4O4S: 617.2 (M+H+); Found: 617.2 (M+H+).

Workup

  1. customThe mixture was purged with nitrogen
  2. additionThe mixture was diluted with EtOAc
  3. washwas washed with water and brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationConcentration and purification by flash column chromatography (hexanes/EtOAc)

Sources & evidence

ORD record
ord-0ce523c6f59c457cb2f452b5c6dc8ad3
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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