Triphenylphosphine → HCID 66604324, compound

HRID 2410845Notes

Reaction equation

HRID 2410845 reaction equation
N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:32][C:33]1[CH:34]=[C:35]([C:40]2[CH:41]=[C:42]([C:59]([NH2:61])=[O:60])[C:43]3[NH:44][C:45]4[CH:46]=[C:47]([N:53]5[CH2:58][CH2:57][O:56][CH2:55][CH2:54]5)[CH:48]=[CH:49][C:50]=4[C:51]=3[N:52]=2)[CH:36]=[CH:37][C:38]=1[OH:39].[O:62]1[CH2:67][CH2:66][N:65]([CH2:68][CH2:69]O)[CH2:64][CH2:63]1>C1COCC1>[Cl:32][C:33]1[CH:34]=[C:35]([C:40]2[CH:41]=[C:42]([C:59]([NH2:61])=[O:60])[C:43]3[NH:44][C:45]4[CH:46]=[C:47]([N:53]5[CH2:54][CH2:55][O:56][CH2:57][CH2:58]5)[CH:48]=[CH:49][C:50]=4[C:51]=3[N:52]=2)[CH:36]=[CH:37][C:38]=1[O:39][CH2:69][CH2:68][N:65]1[CH2:66][CH2:67][O:62][CH2:63][CH2:64]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 136337373HCID 136337373, compound

Product 1

HCID 66604324HCID 66604324, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (0.012 mL, 0.074 mmol) was added to a solution of triphenylphosphine (19 mg, 0.074 mmol), 2-(3-chloro-4-hydroxyphenyl)-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (16 mg, 0.037 mmol) and 2-morpholinoethanol (9.0 μL, 0.074 mmol) in dry THF (0.5 mL) at RT under nitrogen. After stirring overnight, the solvent was removed and preparative HPLC (PHENOMENEX® Luna C18 30×100 10u Column, Solvent A=10 mM NH4OAc in 95% water:5% acetonitrile; B=10 mM NH4OAc in 5% water:95% acetonitrile, gradient of 10 to 100% B over 25 min at 30 mL/min) followed by SCX capture and release with 2 N NH3 in MeOH afforded 2-(3-chloro-4-(2-morpholinoethoxy)phenyl)-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (4.9 mg, 8.2 nmol, 22% yield) as a solid. MS (ESI) m/z 536.38 (M+H). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.26 (1H, s), 8.54 (1H, s), 8.34 (1H, d, J=2.01 Hz), 8.27 (1H, s), 8.21 (1H, dd, J=8.69, 2.14 Hz), 8.07 (1H, d, J=8.56 Hz), 7.84 (1H, s), 7.32 (1H, d, J=8.81 Hz), 7.20 (1H, d, J=2.01 Hz), 7.00 (1H, dd, J=8.81, 2.01 Hz), 4.26 (2H, t, J=5.79 Hz), 3.74-3.85 (4H, m), 3.53-3.66 (4H, m), 3.18-3.28 (4H, m), 2.78 (2H, t, J=5.67 Hz), 2.52-2.59 (4H, m).

Workup

  1. customthe solvent was removed
  2. custompreparative HPLC (PHENOMENEX® Luna C18 30×100 10u Column, Solvent A=10 mM NH4OAc in 95% water:5% acetonitrile; B=10 mM NH4OAc in 5% water:95% acetonitrile, gradient of 10 to 100% B over 25 min at 30 mL/min)

Sources & evidence

ORD record
ord-53a36f794e5b4967a329a5da944bdcd5
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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