Thiomorpholine 1,1-dioxide → HCID 66604564, compound

HRID 2410874Notes

Reaction equation

HRID 2410874 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([F:28])[CH:21]=2)[CH:7]=[C:8]2[C:16]=1[NH:15][C:14]1[CH:13]=[C:12]([C:17]([O-:19])=O)[CH:11]=[CH:10][C:9]2=1)(=[O:3])[NH2:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:53]1[CH2:58][CH2:57][S:56](=[O:60])(=[O:59])[CH2:55][CH2:54]1>CN(C1C=CN=CC=1)C.CN(C=O)C>[F:28][C:22]1[CH:21]=[C:20]([C:6]2[CH:5]=[C:4]([C:1]([NH2:2])=[O:3])[C:16]3[NH:15][C:14]4[C:9]([C:8]=3[CH:7]=2)=[CH:10][CH:11]=[C:12]([C:17]([N:53]2[CH2:58][CH2:57][S:56](=[O:60])(=[O:59])[CH2:55][CH2:54]2)=[O:19])[CH:13]=4)[CH:25]=[CH:24][C:23]=1[O:26][CH3:27]

Participants

6

Reactant 3

HCID 6484228Thiomorpholine 1,1-dioxideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86663070HCID 86663070, compound

Product 1

HCID 66604564HCID 66604564, compoundYield 63.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

8-Carbamoyl-6-(3-fluoro-4-methoxyphenyl)-9H-carbazole-2-carboxylic acid (Example 395, 35 mg, 0.083 mmol), HATU (150 mg, 0.394 mmol), DMAP (50 mg, 0.409 mmol), Thiomorpholine-1,1-dioxide (90 mg, 0.666 mmol) and DMF (2 ml) were combined and stirred at room temperature for 3 days. The reaction mixture was filtered through a 0.45 um Nylon filter and purify by preparative HPLC. Product containing fractions were evaporated to give 26.3 mg 3-(3-fluoro-4-methoxyphenyl)-7-(1,1-dioxo-thiomorpholine-4-carbonyl)-9H-carbazole-1-carboxamide. MS (ESI) m/e+=496, m/e−=494, consistent with [M+H]+and [M−H]− resp. HPLC retention time 9.61 min. (Sunfire C18 3.5 μm, 4.6×150 mm column, 15 min gradient, 10-100% B, 1 mL/min. Solvent A: 5% CH3CN—95% H2O—0.1% TFA; Solvent B: 95% CH3CN—5% H2O—0.1% TFA). 1H NMR (DMSO-d6) δ ppm 11.60 (s, 1H), 8.73 (d, 1H, J=1.6), 8.39 (b, 1H), 8.34-8.30 (m, 2H), 7.86 (d, 1H, J=0.7), 7.81 (dd, 1H, J=13.3, 2.3), 7.71 (dd, 1H, J=8.5, 1.2), 7.60 (b, 1H), 7.35 (dd, 1H, J=8.1, 1.4), 7.31 (t, 1H, J=9.0), 3.92 (s, 3H), 4.2-3.7 (b, 4H), 3.35-3.25 (b, 4H).

Workup

  1. filtrationThe reaction mixture was filtered through a 0.45 um Nylon
  2. filtrationfilter
  3. custompurify by preparative HPLC
  4. additionProduct containing fractions
  5. customwere evaporated

Sources & evidence

ORD record
ord-506abed41c4b441695e21b4be5b05327
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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