Water → 4-(2-Fluorophenyl)-7-(tetrahydro-2H-pyran-4-ylamino)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361264Notes

Reaction equation

HRID 2361264 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[C:14]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[F:21])=[CH:13][N:12]=[C:11]([C:22]([NH2:24])=[O:23])[C:7]=3[NH:8]2)=[CH:4][CH:3]=1.[O:25]1[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>O1CCCC1.ClCCl.C(OCC)(=O)C>[F:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[C:14]1[C:6]2[C:5]3[C:9](=[CH:10][C:2]([NH:1][CH:28]4[CH2:29][CH2:30][O:25][CH2:26][CH2:27]4)=[CH:3][CH:4]=3)[NH:8][C:7]=2[C:11]([C:22]([NH2:24])=[O:23])=[N:12][CH:13]=1

Participants

8

Reactant 4

HCID 962WaterHCID 121599Tetrahydro-4H-pyran-4-one2×HCID 5049666Sodium triacetoxyborohydride2×HCID 679945367-amino-4-(2-fluorophenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

Product 1

HCID 706513764-(2-Fluorophenyl)-7-(tetrahydro-2H-pyran-4-ylamino)-9H-pyrido[3,4-b]indole-1-carboxamideYield 30.9%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 7-amino-4-(2-fluorophenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (30.0 mg, 0.094 mmol), dihydro-2H-pyran-4(3H)-one (10.37 μL, 0.112 mmol), and sodium triacetoxyborohydride (39.7 mg, 0.187 mmol) in tetrahydrofuran (1 mL) and dichloromethane (1 mL) was stirred at rt for 16 hr. Additional dihydro-2H-pyran-4(3H)-one (10.37 μL, 0.112 mmol) and sodium triacetoxyborohydride (39.7 mg, 0.187 mmol) were added, and the mixture was stirred at room temperature for another 8 hr. To the reaction mixture was added water (2 mL), and the resulting mixture was stirred at room temperature for 20 min. It was diluted with ethyl acetate (50 mL), washed with saturated NaHCO3 solution (15 mL) and brine (15 mL), and dried over anhydrous MgSO4. Solvent was removed under vacuum, and the residue was subjected to prep. reverse phase HPLC purification. The correct fraction was concentrated under vacuum and basified with saturated NaHCO3 solution. The precipitating product (11.8 mg, 0.029 mmol, 30.8% yield) was collected as a yellow solid by suction filtration and dried at 50° C. under vacuum. LCMS (M+H)+=405.17. 1H NMR (500 MHz, DMSO-d6) δ: 11.30 (s, 1H), 8.23 (s, 1H), 8.11 (s, 1H), 7.70 (s, 1H), 7.65-7.61 (m, 2H), 7.49-7.42 (m, 2H), 6.98 (d, J=8.0 Hz, 1H), 6.94 (s, 1H), 6.46 (dd, J1=8.7 Hz, J2=1.5 Hz, 1H), 6.19 (br. s, 1H), 3.90 (m, 2H), 3.47 (m, 1H), 3.43 (m, 2H), 1.94 (m, 2H), 1.44 (m, 2H).

Workup

  1. stirringthe mixture was stirred at room temperature for another 8 hr
  2. stirringthe resulting mixture was stirred at room temperature for 20 min
  3. washwashed with saturated NaHCO3 solution (15 mL) and brine (15 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. customSolvent was removed under vacuum
  6. customphase HPLC purification
  7. concentrationThe correct fraction was concentrated under vacuum

Sources & evidence

ORD record
ord-0425ae3ffe3c445fa951adf48e8b7b07
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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