Indole-2-carboxylic acid → HCID 118023274, compound

HRID 706376Notes

Reaction equation

HRID 706376 reaction equation
[NH2:1][CH:2]1[CH2:7][C@@H:6]([C:8]2[C:13]([F:14])=[CH:12][CH:11]=[C:10]([F:15])[C:9]=2[F:16])[C@@H:5]([CH3:17])[N:4]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:3]1=[O:23].[NH:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[C:25]1[C:33]([OH:35])=[O:34]>C(OC(C)C)(=O)C.C1COCC1.ClC1C(O)=C(C=C(Cl)C=1)C=O>[NH:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[C:25]1[C:33]([O-:35])=[O:34].[CH3:17][C@H:5]1[N:4]([CH2:18][C:19]([F:20])([F:22])[F:21])[C:3](=[O:23])[C@@H:2]([NH3+:1])[CH2:7][C@H:6]1[C:8]1[C:13]([F:14])=[CH:12][CH:11]=[C:10]([F:15])[C:9]=1[F:16]

Participants

6

Reactant 2

HCID 72899Indole-2-carboxylic acidHCID 89821845HCID 89821845, compound

Product 1

HCID 118023274HCID 118023274, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 666603,5-DichlorosalicylaldehydeCatalystHCID 7915Isopropyl AcetateSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
57.5 °C

Procedure

To a mixture of crude material containing 24 (2.00 g, 5.88 mmol) and 3,5-dichloro-2-hydroxybenzaldehyde (0.011 g, 0.059 mmol) in isopropyl acetate (15.0 ml) at 55-60° C. under nitrogen was slowly added a solution of 1H-indole-2-carboxylic acid (0.96 g, 5.88 mmol) in THF (10.0 ml) over 2 hours. Upon completion of acid addition, a thick salt suspension was agitated at 55-60° C. for another 18 h and then was allowed to cool to ambient temperature. The salt was filtered and washed with isopropyl acetate. After drying at 60° C. in a vacuum oven with nitrogen purge for 8 h, 26 (2.33 g, 79.0%) was isolated as crystals. 1H NMR (500 MHz, DMSO): δ 11.40 (s, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.45 (br, 3H), 7.47 (ddd, J=14.8, 10.1, 8.3 Hz, 1H), 7.41-7.40 (m, 1H), 7.16-7.14 (m, 2H), 6.98-6.97 (m, 1H), 6.87 (s, 1H), 4.69 (dq, J=15.3, 9.6 Hz, 1H), 3.84-3.81 (m, 4H), 2.76-2.71 (m, 1H), 2.34 (dd, J=12.7, 6.3 Hz, 1H), 1.13 (d, J=6.5 Hz, 3H); 13C NMR (100 MHz, DMSO-d6): δ 170.9, 164.8, 156.8 (ddd, J=244, 7.0, 2.5 Hz), 149.1 (ddd, J=249, 14.4, 8.5 Hz), 147.2 (ddd, J=246, 13.9, 3.2 Hz), 137.0, 133.5, 127.8, 125.4 (q, J=282 Hz), 123.3, 121.8, 119.7, 117.8 (dd, J=19.8, 13.8 Hz), 117.2 (dd, J=19.2, 10.6 Hz), 112.7, 112.3 (ddd, J=26.1, 6.7, 3.3 Hz), 105.1, 57.1, 51.3, 44.8 (q, J=32.7 Hz), 35.2, 26.9, 14.5.

Workup

  1. additionTo a mixture of crude material
  2. additionUpon completion of acid addition
  3. temperatureto cool to ambient temperature
  4. filtrationThe salt was filtered
  5. washwashed with isopropyl acetate
  6. customAfter drying at 60° C. in a vacuum oven with nitrogen
  7. custompurge for 8 h

Sources & evidence

ORD record
ord-a5612562dc22498583d4ac98cd82d36a
Source dataset
uspto-grants-2015_11
Patent number
US09174989B2

Reaction notes

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