Potassium Carbonate → (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-6-yl)benzo[d]thiazol-6-yl)acetate

HRID 879491Notes

Reaction equation

HRID 879491 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[S:12][C:13]4[C:19]([C:20]5[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=5)=[C:18]([C@H:27]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:17]([CH3:38])=[CH:16][C:14]=4[N:15]=3)=[CH:8][CH:9]=2)[N:4]([CH3:39])[N:3]=1.[CH3:40][N:41]1[CH2:46][CH:45]=[C:44](B2OC(C)(C)C(C)(C)O2)[CH2:43][CH2:42]1.C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[C:34]([O:33][C@@H:27]([C:18]1[C:17]([CH3:38])=[CH:16][C:14]2[N:15]=[C:11]([C:7]3[CH:6]=[C:5]4[C:10]([C:2]([C:44]5[CH2:45][CH2:46][N:41]([CH3:40])[CH2:42][CH:43]=5)=[N:3][N:4]4[CH3:39])=[CH:9][CH:8]=3)[S:12][C:13]=2[C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1)[C:28]([O:30][CH2:31][CH3:32])=[O:29])([CH3:37])([CH3:36])[CH3:35]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 207733711-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 86700308(S)-ethyl 2-(2-(3-bromo-1-methyl-1H-indazol-6-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

Product 1

HCID 86700307(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-6-yl)benzo[d]thiazol-6-yl)acetate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with (S)-ethyl 2-(2-(3-bromo-1-methyl-1H-indazol-6-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (36 mg, 57 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (13 mg, 57 mmol), KHCO3 (6.3 mg, 63 μmol), Pd(PPh3)4 (6.7 mg, 5.7 mmol), 2 M aq K2CO3 (250 mL), and dioxane (1 mL). The vessel was sealed and heated to 100° C. for 1 h. The reaction was cooled to 23° C., and filtered (0.45 micron teflon syringe filter). The filtrate was purified by reverse phase HPLC, eluting by 5-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+: calc'd for C36H39ClN4O3S: 643.2, 645.2 (M+H+); Found: 643.0, 645.0 (M+H+). 1H NMR (400 MHz, CD3OD): δ 8.27 (s, 1H), 8.10 (d, J=8.7 Hz, 1H), 7.97-7.82 (m, 2H), 7.72-7.48 (m, 4H), 6.61 (s, 1H), 5.27 (s, 1H), 4.38-4.18 (m, 2H), 4.14 (s, 3H), 4.06-3.93 (m, 2H), 3.65-3.46 (m, 1H), 3.21-3.07 (m, 3H), 3.03 (s, 3H), 2.61 (s, 3H), 1.26 (t, J=7.1 Hz, 3H), 1.00 (s, 9H).

Workup

  1. customThe vessel was sealed
  2. temperatureThe reaction was cooled to 23° C.
  3. filtrationfiltered
  4. filtration(0.45 micron teflon syringe filter)
  5. customThe filtrate was purified by reverse phase HPLC
  6. washeluting by 5-100% acetonitrile in H2O with 0.1% TFA

Sources & evidence

ORD record
ord-d22aee6c82d34e6a90cedb014fbdc69a
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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