Sodium Carbonate → ethyl 4-(8-chloro-5-methylchroman-6-yl)-9-cyclopropyl-2-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indole-3-carboxylate

HRID 1912637Notes

Reaction equation

HRID 1912637 reaction equation
[CH:1]1([N:4]2[C:12]3[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=3[C:6]3[C:13](OS(C(F)(F)F)(=O)=O)=[C:14]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:15]([CH3:17])=[N:16][C:5]2=3)[CH2:3][CH2:2]1.[Cl:31][C:32]1[CH:33]=[C:34](B2OC(C)(C)C(C)(C)O2)[C:35]([CH3:42])=[C:36]2[C:41]=1[O:40][CH2:39][CH2:38][CH2:37]2.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[Cl:31][C:32]1[CH:33]=[C:34]([C:13]2[C:6]3[C:7]4[CH2:8][CH2:9][CH2:10][CH2:11][C:12]=4[N:4]([CH:1]4[CH2:3][CH2:2]4)[C:5]=3[N:16]=[C:15]([CH3:17])[C:14]=2[C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:35]([CH3:42])=[C:36]2[C:41]=1[O:40][CH2:39][CH2:38][CH2:37]2

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 595785552-(8-Chloro-5-methylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86675746HCID 86675746, compound

Product 1

HCID 71209267ethyl 4-(8-chloro-5-methylchroman-6-yl)-9-cyclopropyl-2-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indole-3-carboxylateYield 95.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of ethyl 9-cyclopropyl-2-methyl-4-(((trifluoromethyl)sulfonyl)oxy)-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indole-3-carboxylate (500 mg, 1.120 mmol), 2-(8-chloro-5-methylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.415 g, 1.344 mmol), and Na2CO3 (0.356 g, 3.36 mmol) in 1,4-dioxane (8.8 ml) and water (2.2 ml) was degassed with N2 for 5 min, treated with Pd(Ph3P)4 (0.129 g, 0.112 mmol), degassed with N2 for 5 min, and then heated to 90° C. for 2 hours. The reaction was cooled to rt, diluted with water, extracted with EtOAc 2×, washed with Brine, dried with Na2SO4, filtered, and concentrated. Purification with column chromatography (0-40% EtOAc/Hexane) gave ethyl 4-(8-chloro-5-methylchroman-6-yl)-9-cyclopropyl-2-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indole-3-carboxylate (510.8 mg, 1.066 mmol, 95% yield) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.00 (s, 1 H), 4.33-4.23 (m, 2 H), 4.03 (q, J=7.1 Hz, 2 H), 3.17-3.06 (m, 1 H), 2.80 (t, J=5.9 Hz, 2 H), 2.74-2.61 (m, 5 H), 2.17-2.06 (m, 2 H), 1.91-1.70 (m, 7 H), 1.65-1.57 (m, 2 H), 1.20-1.06 (m, 4 H), 0.98 (t, J=7.1 Hz, 3 H); LCMS (m/z) ES+=479 (M+1).

Workup

  1. customwas degassed with N2 for 5 min
  2. customdegassed with N2 for 5 min
  3. temperatureThe reaction was cooled to rt
  4. additiondiluted with water
  5. extractionextracted with EtOAc 2×
  6. washwashed with Brine
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification with column chromatography (0-40% EtOAc/Hexane)

Sources & evidence

ORD record
ord-7928bd0b12e44a95a18b220ce31eb5d2
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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