Ammonia → HCID 66604967, compound

HRID 2410834Notes

Reaction equation

HRID 2410834 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:22]([NH2:24])=[O:23])[C:5]2[NH:6][C:7]3[CH:8]=[C:9]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][C:16]4=[O:21])[CH:10]=[CH:11][C:12]=3[C:13]=2[N:14]=1.CC1(C)C(C)(C)OB([C:33]2[S:37][C:36]([CH2:38][N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[CH:35][CH:34]=2)O1.C([O-])([O-])=O.[Na+].[Na+].C(O)(C(F)(F)F)=O.N>CN(C=O)C.CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O.COCCOC>[O:42]1[CH2:43][CH2:44][N:39]([CH2:38][C:36]2[S:37][C:33]([C:2]3[CH:3]=[C:4]([C:22]([NH2:24])=[O:23])[C:5]4[NH:6][C:7]5[CH:8]=[C:9]([N:15]6[CH2:20][CH2:19][O:18][CH2:17][C:16]6=[O:21])[CH:10]=[CH:11][C:12]=5[C:13]=4[N:14]=3)=[CH:34][CH:35]=2)[CH2:40][CH2:41]1

Participants

11

Reactant 5

HCID 222AmmoniaHCID 6422Trifluoroacetic acid2×HCID 10340Sodium CarbonateHCID 467390464-((5-(Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl)methyl)morpholineHCID 86663057HCID 86663057, compound

Product 1

HCID 66604967HCID 66604967, compoundYield 60%

Reagents, catalysts & solvents 5

HCID 178418807HCID 178418807, compoundCatalystHCID 887MethanolSolvent3×HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-bromo-7-(3-oxomorpholino)-5H-pyrido[3,2-b]indole-4-carboxamide (30 mg, 0.077 mmol), 4-((5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl)methyl)morpholine (48 mg, 0.15 mmol), PdCl2(dppf)-CH2Cl2 adduct (6 mg, 8 μmol) was flushed with nitrogen. DME (1.5 mL) and Na2CO3 (0.19 mL, 0.39 mmol, 2.0 N aq. solution) were added and the vial was sealed and heated at 100° C. for 2 hrs. This was diluted with DMF and preparative HPLC (100×30 mm Luna C18 column, Solvent A=10% Methanol, 90% H2O, 0.1% TFA; Solvent B=90% Methanol, 10% H2O, 0.1% TFA, 10-60% B at 42 mL/min over 20 min) followed by SCX capture and release with 2 N NH3 in MeOH afforded 2-(5-(morpholinomethyl)thiophen-2-yl)-7-(3-oxomorpholino)-5H-pyrido[3,2-b]indole-4-carboxamide (23 mg, 0.046 mmol, 60% yield) as a yellow solid. MS (ESI) m/z 492.15 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.67 (1H, s), 8.54 (1H, s), 8.37 (1H, s), 8.20 (1H, d, J=8.24 Hz), 7.92(1H, s), 7.74 (1H, d, J=1.83 Hz), 7.67 (1H, d, J=3.66 Hz), 7.30 (1H, dd, J=8.24, 1.83 Hz), 7.05 ( 1H, d, J=3.66 Hz), 4.27 (2H, s), 4.01-4.07 (2H, m), 3.79-3.88 (2H, m), 3.73 (2H, s), 3.63 (4H, t, J=4.73 Hz), 2.47 (4H, br. s.).

Workup

  1. customwas flushed with nitrogen
  2. customthe vial was sealed

Sources & evidence

ORD record
ord-76b484aecd9e45e698c7ad40a5f4de97
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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