Benzothiazole-6-carbonitrile → tert-Butyl 4-((6-cyanobenzo[d]thiazol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

HRID 2174088Notes

Reaction equation

HRID 2174088 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]2[N:7]=[CH:8][S:9][C:5]=2[CH:4]=1)#[N:2].CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C.[CH:32]([C:34]1[C:42]([O:43][CH3:44])=[CH:41][C:40]([CH3:45])=[C:39]2[C:35]=1[CH:36]=[CH:37][N:38]2[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])=[O:33]>C1COCC1.[Li+].CC([N-]C(C)C)C>[C:1]([C:3]1[CH:11]=[CH:10][C:6]2[N:7]=[C:8]([CH:32]([OH:33])[C:34]3[C:42]([O:43][CH3:44])=[CH:41][C:40]([CH3:45])=[C:39]4[C:35]=3[CH:36]=[CH:37][N:38]4[C:46]([O:48][C:49]([CH3:51])([CH3:50])[CH3:52])=[O:47])[S:9][C:5]=2[CH:4]=1)#[N:2]

Participants

6

Reactant 3

HCID 10607144Benzothiazole-6-carbonitrileHCID 22742125Tetrahydrofuran heptane ethylbenzolHCID 72191522tert-Butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701724tert-Butyl 4-((6-cyanobenzo[d]thiazol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 2724682Lithium diisopropylamideSolvent

Procedure

To a solution of 6-cyanobenzothiazol (CAS #:58249-61-9) (54.60 mg, 0.341 mmol) in THF (1.06 mL), LDA in Heptane/THF/Ethylbenzene (205 uL, 0.409 mmol) was added at −78° C. After 20 mins, a solution of tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 19-D) (79 mg, 0.273 mmol) in THF (1.68 mL) was added to the reaction mixture at −78° C. After stirring for 1.5 h, the reaction was quenched with MeOH, sat. aq. NH4Cl solution and brine. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, concentrated, and purified using FCC eluting with Heptane/EtOAc to provide the title compound. MS (ESI−) m/z 448 (M−H).

Workup

  1. customthe reaction was quenched with MeOH, sat. aq. NH4Cl solution and brine
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified
  8. washeluting with Heptane/EtOAc

Sources & evidence

ORD record
ord-babb7957472c46a49844c1d1331221d8
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

Loading…