Ammonia → HCID 66604529, compound

HRID 2410839Notes

Reaction equation

HRID 2410839 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:21]([NH2:23])=[O:22])[C:5]2[NH:6][C:7]3[CH:8]=[C:9]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[CH:10]=[CH:11][C:12]=3[C:13]=2[N:14]=1.[Cl:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][C:30]=1[O:31][CH3:32].C([O-])([O-])=O.[Na+].[Na+].C(O)(C(F)(F)F)=O.N>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>[Cl:24][C:25]1[CH:26]=[C:27]([C:2]2[CH:3]=[C:4]([C:21]([NH2:23])=[O:22])[C:5]3[NH:6][C:7]4[CH:8]=[C:9]([N:15]5[CH2:20][CH2:19][O:18][CH2:17][CH2:16]5)[CH:10]=[CH:11][C:12]=4[C:13]=3[N:14]=2)[CH:28]=[CH:29][C:30]=1[O:31][CH3:32]

Participants

10

Reactant 5

HCID 222AmmoniaHCID 6422Trifluoroacetic acid2×HCID 10340Sodium CarbonateHCID 32475223-Chloro-4-methoxybenzeneboronic acidHCID 86663061HCID 86663061, compound

Product 1

HCID 66604529HCID 66604529, compoundYield 19.2%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

Procedure

A mixture of 2-bromo-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (50 mg, 0.120 mmol), 3-chloro-4-methoxyphenylboronic acid (33.5 mg, 0.180 mmol), PdCl2(dppf)-CH2Cl2 adduct (9.8 mg, 0.012 mmol) in a microwave vial was flushed with nitrogen. DME (2 mL) and aq. Na2CO3 solution (0.30 mL, 0.60 mmol, 2.0 M) were added and the vial was sealed and heated at 100° C. for 3.5 hr. 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 to 70% gradient over 20 min at 42 mL/min) followed by SCX capture and release with 2 N NH3 in MeOH gave 2-(3-chloro-4-methoxyphenyl)-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (10 mg, 0.023 mmol, 19% yield) as a solid. MS (ESI) m/z 437.21 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.24 (1H, s), 8.53 (1H, s), 8.35 (1H, d, J=2.14 Hz), 8.27 (1H, s), 8.24 (1H, dd, J=8.55, 2.14 Hz), 8.08 (1H, d, J=8.85 Hz), 7.82 (1H, s), 7.31 (1H, d, J=8.85 Hz), 7.22 (1H, d, J=2.14 Hz), 7.01 (1H, dd, J=8.55, 2.14 Hz), 3.95 (3H, s), 3.78-3.85 (4H, m), 3.22-3.27 (4H, m).

Workup

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

Sources & evidence

ORD record
ord-34d35a3f932a457b94673b276a54097c
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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