Acetic Acid → HCID 59375142, compound

HRID 1811161Notes

Reaction equation

HRID 1811161 reaction equation
[NH2:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[C:7]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([NH:24][C:25](=[O:33])[C:26]5[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=5)[C:19]=4[CH3:34])=[CH:8][CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1.[CH3:35][C:36]([CH3:38])=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[F:32][C:29]1[CH:28]=[CH:27][C:26]([C:25]([NH:24][C:20]2[C:19]([CH3:34])=[C:18]([C:7]3[C:6]4[C:5]5[C:13](=[CH:14][C:2]([NH:1][CH:36]([CH3:38])[CH3:35])=[CH:3][CH:4]=5)[NH:12][C:11]=4[C:10]([C:15]([NH2:17])=[O:16])=[CH:9][CH:8]=3)[CH:23]=[CH:22][CH:21]=2)=[O:33])=[CH:31][CH:30]=1

Participants

7

Reactant 5

HCID 176Acetic Acid2×HCID 180AcetoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 59375083HCID 59375083, compound

Product 1

HCID 59375142HCID 59375142, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
40 °C

Procedure

A suspension of 7-amino-4-(3-(4-fluorobenzamido)-2-methylphenyl)-9H-carbazole-1-carboxamide (Example 54-5, 1 g, 2.210 mmol), acetone (3.4 mL, 20 eq.), and acetic acid (0.443 mL, 7.74 mmol) in 1,2-dichloroethane (220 mL) was treated with sodium triacetoxyborohydride (1.639 g, 7.74 mmol) and stirred at 40° C. for 4 h. Additional sodium triacetoxyborohydride (520 mg, 1.1 eq) and acetic acid (0.19 mL, 1.5 eq) were added and the mixture was stirred overnight. The mixture was treated with NaHCO3 (aq) and the organic phase was separated, washed with brine, dried and concentrated. The residue was purified by preparative HPLC. The appropriate effluent fractions were made basic with NaHCO3 (aq) and extracted with EtOAc. The organic phase was washed with brine, dried and concentrated. The residue was triturated with methanol to provide 4-(3-(4-fluorobenzamido)-2-methylphenyl)-7-(isopropylamino)-9H-carbazole-1-carboxamide as an off-white solid (520 mg, 48%). 1H NMR (400 MHz, DMSO-d6) δ 11.01 (1 H, s), 10.09 (1 H, s), 8.07 (3 H, dd, J=8.8, 5.3 Hz), 7.77 (1 H, d, J=7.9 Hz), 7.27-7.51 (5 H, m), 7.17 (1 H, d, J=6.2 Hz), 6.73-6.88 (2 H, m), 6.60 (1 H, d, J=8.3 Hz), 6.23 (1 H, dd, J=8.8, 2.2 Hz), 5.49 (1 H, d, J=7.9 Hz), 3.53 (1H, dd, J=13.8, 6.4 Hz), 1.90 (3 H, s), 1.04-1.21 (6 H, m). Mass spectrum m/z 495.1 (M+H)+.

Workup

  1. stirringthe mixture was stirred overnight
  2. customthe organic phase was separated
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC
  7. extractionextracted with EtOAc
  8. washThe organic phase was washed with brine
  9. customdried
  10. concentrationconcentrated
  11. customThe residue was triturated with methanol

Sources & evidence

ORD record
ord-0e0e812de7694206acba048545310cec
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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