Hydrochloric Acid → (S)-1'-(tert-butyl)-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylic acid

HRID 706399Notes

Reaction equation

HRID 706399 reaction equation
[C:1]([N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C@:7]2([CH2:22][C:16]3=[N:17][CH:18]=[C:19](Cl)[CH:20]=[C:15]3[CH2:14]2)[C:6]1=[O:23])([CH3:4])([CH3:3])[CH3:2].[C:24]([O-])([O-:26])=[O:25].[K+].[K+].Cl>CN1C(=O)CCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2CCCCC2)CCCP(C2CCCCC2)C2CCCCC2)CCCCC1>[C:1]([N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C@:7]2([CH2:22][C:16]3=[N:17][CH:18]=[C:19]([C:24]([OH:26])=[O:25])[CH:20]=[C:15]3[CH2:14]2)[C:6]1=[O:23])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 89821832(S)-1'-(tert-butyl)-3-chloro-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Product 1

HCID 89821793(S)-1'-(tert-butyl)-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylic acidYield 95%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 4388761,3-Bis(dicyclohexylphosphino)propaneCatalystHCID 962WaterSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 58 (5.0 g, 14.5 mmol), K2CO3 (5.01 g, 36.2 mmol), Pd(OAc)2 (33 mg, 0.145 mmol), 1,3-bis(dicyclohexylphosphino)propane (DCPP, 127 mg, 0.290 mmol) and water (0.522 mL, 29.0 mmol) in NMP (32 mL) was heated at 120° C. under 30 psi of CO for 24 h. After cooling to room temperature, the resulting slurry was diluted with water (100 mL). The pH was slowly adjusted to 3-4 with 2 N HCl. The slurry was aged at room temperature for 1 h, filtered, rinsed with water (40 to 50 mL), dried under oven at 60° C. to give 59 (4.64 g, 95%) as a solid. 1H NMR (DMSO-d6, 500 MHz): δ 8.90 (s, 1H), 8.19 (d, J=5.2 Hz, 1H), 7.54 (d, J=7.3 Hz, 1H,), 6.99 (dd, J=7.3, 5.2 Hz, 1H), 3.33 (m, 4H), 1.72 (s, 9H); 13C NMR (DMSO-d6, 125 MHz): δ 180.16, 167.44, 166.97, 158.07, 149.76, 146.61, 135.39, 133.09, 130.36, 128.81, 125.48, 118.44, 58.19, 51.12, 44.56, 41.24, 28.91.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationfiltered
  3. washrinsed with water (40 to 50 mL)
  4. customdried under oven at 60° C.

Sources & evidence

ORD record
ord-284c24324c0048aaa4449edcf8a246c8
Source dataset
uspto-grants-2015_11
Patent number
US09174989B2

Reaction notes

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