Ammonia → HCID 66604891, compound

HRID 2410830Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]=[C:13](Br)[CH:12]=[C:11]([C:16]([NH2:18])=[O:17])[C:7]=3[NH:8][C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:27]2[CH:39]=[CH:38][C:30]([CH2:31][N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[CH:29][CH:28]=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>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]=[C:13]([C:27]4[CH:28]=[CH:29][C:30]([CH2:31][N:32]5[CH2:37][CH2:36][O:35][CH2:34][CH2:33]5)=[CH:38][CH:39]=4)[CH:12]=[C:11]([C:16]([NH2:18])=[O:17])[C:7]=3[NH:8][C:9]=2[CH:10]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A microwave vial containing 7-amino-2-bromo-5H-pyrido[3,2-b]indole-4-carboxamide (150 mg, 0.393 mmol), 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)morpholine (238 mg, 0.787 mmol), PdCl2(dppf)-CH2Cl2 adduct (32 mg, 0.039 mmol) was flushed with nitrogen. DME (2 mL) and Na2CO3 (0.98 mL, 2.0 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 7-amino-2-(4-(morpholinomethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (90 mg, 0.20 mmol, 51% yield) as a yellow solid. MS (ESI) m/z 402.16 (M+H); HPLC retention time of 0.87 min with Xbridge S10 4.6×50 mm column, 3 min gradient, 0-100% B, 4 mL/min. Solvent A: 95% MeOH—5% H2O—0.1% TFA; Solvent B: 5% MeOH—95% H2O—0.1% TFA.

Workup

customwas flushed with nitrogen
customthe vial was sealed

Sources & evidence

ORD record: ord-08df315c078d4a65b54a9f9791ece0ff
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815840B2

Reaction notes

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