HCID 66606694, compound → HCID 46834101, compound

HRID 1811088Notes

Reaction equation

HRID 1811088 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]([C:27]2[S:31][C:30]([N:32]([CH:40]([CH3:42])[CH3:41])C(=O)OC(C)(C)C)=[N:29][CH:28]=2)=[C:8]2[C:16]=1[NH:15][C:14]1[CH2:13][CH:12]([C:17](=[O:26])[NH:18][CH:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[CH2:11][CH2:10][C:9]2=1)(=[O:3])[NH2:2]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH:40]([NH:32][C:30]1[S:31][C:27]([C:7]2[CH:6]=[CH:5][C:4]([C:1]([NH2:2])=[O:3])=[C:16]3[C:8]=2[C:9]2[CH2:10][CH2:11][CH:12]([C:17]([NH:18][CH:19]4[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]4)=[O:26])[CH2:13][C:14]=2[NH:15]3)=[CH:28][N:29]=1)([CH3:42])[CH3:41]

Participants

4

Reactant 1

HCID 66606694HCID 66606694, compound

Product 1

HCID 46834101HCID 46834101, compoundYield 61.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl 5-(8-carbamoyl-2-(1-methylpiperidin-4-ylcarbamoyl)-2,3,4,9-tetrahydro-1H-carbazol-5-yl)thiazol-2-yl(isopropyl)carbamate (Example 3-111, 35 mg, 0.059 mmol) in DCM (1 mL) and TFA (1 mL) was stirred at rt for 2 h. The solution was concentrated and the residue was partitioned between DCM and 1 M aqueous sodium bicarbonate. The organic phase was concentrated and the residue was purified by preparative HPLC. The appropriate effluent fractions were made basic with 1 M aqueous sodium hydroxide, extracted twice with DCM, and the combined organic phases were washed with water, dried and concentrated to provide 5-(2-(isopropylamino)thiazol-5-yl)-N2-(1-methylpiperidin-4-yl)-2,3,4,9-tetrahydro-1H-carbazole-2,8-dicarboxamide (Example 4-1, 18 mg, 61%) as a white solid. 1H NMR (400 MHz, methanol-d4) δ 7.51 (1H, d, J=7.91 Hz), 6.95 (1H, d, J=7.91 Hz), 6.89 (1H, s), 3.81-3.89 (1H, m), 3.64-3.73 (1H, m), 2.79-3.07 (4H, m), 2.59-2.75 (3H, m), 2.27 (3H, s), 2.09-2.18 (2H, m), 1.97-2.06 (1H, m), 1.84-1.92 (2H, m), 1.70-1.83 (1H, m), 1.48-1.61 (2H, m), 1.27 (6H, d, J=6.15 Hz). Mass spectrum m/z 495.2 (M+H)+. Also obtained was 4-(2-(isopropylamino)thiazol-5-yl)-N7-(1-methylpiperidin-4-yl)-9H-carbazole-1,7-dicarboxamide as a white solid (Example 4-2, 5.2 mg, 18%). 1H NMR (400 MHz, methanol-d4) δ 8.04-8.10 (2H, m), 7.88-7.93 (1H, m), 7.52-7.58 (1H, m), 7.25 (1H, s), 7.14-7.20 (1H, m), 3.87-3.98 (2H, m), 2.88-2.97 (2H, m), 2.31 (3H, s), 2.15-2.24 (2H, m), 1.95-2.03 (2H, m), 1.64-1.79 (2H, m), 1.32 (6H, d, J=6.59 Hz). Mass spectrum m/z 491.2 (M+H)+.

Workup

  1. concentrationThe solution was concentrated
  2. customthe residue was partitioned between DCM and 1 M aqueous sodium bicarbonate
  3. concentrationThe organic phase was concentrated
  4. customthe residue was purified by preparative HPLC
  5. extractionextracted twice with DCM
  6. washthe combined organic phases were washed with water
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-9de28084321346a6a130c3666fd0ecd3
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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