Pyridine → HCID 86661425, compound

HRID 1506711Notes

Reaction equation

HRID 1506711 reaction equation
[CH2:1]([N:3]([CH2:23][CH3:24])[C:4]([CH:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[F:19])[N:11]([CH2:20][CH2:21][OH:22])[C:10]=2[CH2:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].C(N(CC)C(C1C2C3C(=CC(F)=CC=3)N(CCO)C=2CCC1)=O)C.N1C=CC=CC=1.[CH3:55][S:56](Cl)(=[O:58])=[O:57]>ClCCl>[CH2:1]([N:3]([CH2:23][CH3:24])[C:4]([CH:6]1[C:18]2[C:13]3[C:12](=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[N:11]([CH2:20][CH2:21][O:22][S:56]([CH3:55])(=[O:58])=[O:57])[C:10]=2[CH2:9][CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 66679593HCID 66679593, compoundHCID 66680058HCID 66680058, compound

Product 1

HCID 86661425HCID 86661425, compoundYield 1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of a mixture of 5-fluoro-9-(2-hydroxy-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide (42) and 7-fluoro-9-(2-hydroxy-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide (743 mg, 2.2 mmol) in dichloromethane (30 mL) was added pyridine (1.74 g, 22.0 mmol, 1.8 mL). The reaction was cooled to 0° C. and methanesulfonyl chloride (1.01 g, 8.8 mmol, 0.7 mL) was added. The reaction was allowed to warm to room temperature overnight. The mixture was washed with 2 N HCl (2×50 mL) and water (2×50 mL), dried and concentrated in vacuo. The crude material was purified by semi preparative HPLC eluting with water (A) and methanol (B) (Gemini 5u, C18, 110A, 150×21 mm, 50-95% B over 20 min, 21 mL/min) to afford 10 mg (1%) of methanesulfonic acid 2-(4-diethylcarbamoyl-7-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl)-ethyl ester as a white solid and 30 mg (9%) of a mixture of methanesulfonic acid 2-(4-diethylcarbamoyl-7-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl)-ethyl ester and methanesulfonic acid 2-(4-diethylcarbamoyl-5-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl)-ethyl ester (precursor compound 10) as a white solid. Using these purification conditions, methanesulfonic acid 2-(4-diethylcarbamoyl-5-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl)-ethyl ester (precursor compound 10) could not be isolated as a single component. The structure of methanesulfonic acid 2-(4-diethylcarbamoyl-7-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl)-ethyl ester was confirmed by 1H NMR (300 MHz, CDCl3) δH 1.18 (3H, t, J=7 Hz, N(CH2CH3)2), 1.39 (3H, t, J=7 Hz, N(CH2CH3)2) 1.70-2.30 (4H, m, 2- and 3-CH2), 2.58 (3H, s, OSO2CH3), 2.60-2.80 (2H, m, 1-CH2), 3.40-3.65 (4H, m, N(CH2CH3)2), 4.02 (1H, t, J=6 Hz, 4-CH), 4.20 (2H, t, J=7 Hz, NCH2CH2O Ms), 4.35 (2H, t, J=7 Hz, NCH2CH2O Ms), 6.70-6.85 (1H, m, NCCHCFCHCH), 6.90-7.00 (1H, m, NCCHCFCHCH), and 7.05-7.15 (2H, m, NCCHCFCHCH).

Workup

  1. temperatureto warm to room temperature overnight
  2. washThe mixture was washed with 2 N HCl (2×50 mL) and water (2×50 mL)
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by semi preparative HPLC
  6. washeluting with water (A) and methanol (B) (Gemini 5u, C18, 110A, 150×21 mm, 50-95% B over 20 min, 21 mL/min)

Sources & evidence

ORD record
ord-2f50d97af7fc47ebb2ad26b3e9fc12c8
Source dataset
uspto-grants-2015_12
Patent number
US09220795B2

Reaction notes

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