Sodium Bicarbonate → HCID 59700203, compound

HRID 2234648Notes

Reaction equation

HRID 2234648 reaction equation
[Cl:1][C:2]1[C:3]([OH:28])=[C:4]([CH:8]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[CH:18][NH:17][C:14]3=[N:15][CH:16]=2)[CH:10]=1)[C:5](O)=[O:6].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[CH3:53][N:54]([CH3:63])[CH2:55][CH2:56][N:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1.C(=O)(O)[O-].[Na+]>C(#N)C.CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([OH:28])=[C:4]([C:5]([N:60]2[CH2:61][CH2:62][N:57]([CH2:56][CH2:55][N:54]([CH3:63])[CH3:53])[CH2:58][CH2:59]2)=[O:6])[CH:8]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[CH:18][NH:17][C:14]3=[N:15][CH:16]=2)[CH:10]=1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 27362291-(2-(Dimethylamino)ethyl)piperazineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 57731641HCID 57731641, compound

Product 1

HCID 59700203HCID 59700203, compoundYield 12.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

30 mg (76 μmol) of 3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoic acid and 46 mg (0.12 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate were dissolved in a mixture of 1.8 mL of acetonitrile and 0.2 mL of DMF. 40 μL (approx. 0.2 mmol; density unknown) of 1-(2-di-methylaminoethyl)-piperazine was added and the resulting mixture heated to 90° C. for 18 h. 40 mg (0.11 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate were added and the mixture heated to 100° C. for 3 days. The resulting mixture was distributed between a saturated aqueous solution of sodium bicarbonate and ethyl acetate. The aqueous layer was extracted three times with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate and evaporated. The resulting crude was purified by mass-triggered reverse-phase HPLC to afford 5.0 mg (9.4 μmol, 12%) of {3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-[4-(2-dimethylamino-ethyl)-piperazin-1-yl]-methanone as an ivory solid. 1H NMR (500 MHz, DMSO-d6) δ 11.91 (s, 1H), 8.49 (d, 1H), 8.12 (d, 1H), 7.77 (d, 1H), 7.73 (d, 1H), 7.63 (dd, 1H), 7.42 (d, 1H), 7.29 (ddd, 1H), 7.13 (d, 1H), 7.06 (ddd, 1H), 3.82 (s, 3H), 3.68-3.50 (m, br. 2H), 3.08-2.90 (m, br., 2H), 2.48-2.3 (m, 8H), 2.13 (s, 6H), MS: m/z 534.2 (M+H+), 548.2 (M+Na+).

Workup

  1. temperaturethe mixture heated to 100° C. for 3 days
  2. extractionThe aqueous layer was extracted three times with ethyl acetate
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customThe resulting crude was purified by mass-triggered reverse-phase HPLC

Sources & evidence

ORD record
ord-00e2c1e2c8f348b4854adcf37042d22c
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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