Dichloromethane → HCID 71270619, compound

HRID 2406277Notes

Reaction equation

HRID 2406277 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C@H:9]2[CH2:13][C@H:12]([OH:14])[C@H:11]([CH2:15][OH:16])[CH2:10]2)[CH:3]=1.Cl.[Cl:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[C@@H:24]([NH2:28])[C@@H:23]([O:29][CH3:30])[CH2:22]2.C(N(CC)C(C)C)(C)C.C(Cl)Cl>CN1CCCC1=O>[Cl:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[C@@H:24]([NH:28][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C@H:9]3[CH2:13][C@H:12]([OH:14])[C@H:11]([CH2:15][OH:16])[CH2:10]3)[CH:3]=1)[C@@H:23]([O:29][CH3:30])[CH2:22]2

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 71270609HCID 71270609, compoundHCID 86686872HCID 86686872, compound

Product 1

HCID 71270619HCID 71270619, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

To a 500 ml Parr pressure vessel was added (1S,2S,4R)-4-(6-chloropyrimidin-4-yloxy)-2-(hydroxymethyl)cyclopentanol (26) (25.00 g, 102.2 mmol) in N-methylpyrrolidinone (200 mL). To this mixture was added (1R,2S)-5-chloro-2-methoxy-2,3-dihydro-1H-inden-1-amine hydrochloride (31.10 g, 132.8 mmol) followed by N,N-diisopropylethylamine (88.99 mL, 510.9 mmol). The vessel was then sealed, pressurised with 30 psi of nitrogen and heated to 130° C. for 22 hours. The pressure increased to 50 psi when the reaction reached temperature and held during the course of the reaction. After 22 hours the reaction was cooled to ambient temperature and the pressure was vented. Methylene chloride (250 mL) was added to the reaction mixture and this was then extracted with saturated sodium bicarbonate in water (250 mL). The organic layer was then extracted four times with water (250 mL) and once with saturated sodium chloride in water (250 mL). The organic layer was then dried over sodium sulfate (7.5 g), filtered and concentrated. To the black semisolid oil was added acetonitrile (250 mL) and the mixture was stirred for 2 hours at ambient temperature. During this time a beige solid precipitated and was filtered and dried under reduced pressure at 40° C. for 16 hours. A light biege solid was afforded (17 g, 41%). 1H NMR (300 MHz, CD3OD, δ): 8.19 (s, 1H), 7.25 (s, 1H), 7.18 (m, 2H), 5.97 (s, 1H), 5.58 (m, 1H), 5.30 (m, 1H), 4.41 (m, 1H), 4.22 (m, 1H), 3.76 (m, 1H), 3.61 (m, 1H), 3.30 (s, 3H), 3.05 (m, 2H), 2.30 (m, 2H) and 1.97 (m, 3H).

Workup

  1. customThe vessel was then sealed
  2. temperatureThe pressure increased to 50 psi when the reaction
  3. customheld during the course of the reaction
  4. temperatureAfter 22 hours the reaction was cooled to ambient temperature
  5. extractionthis was then extracted with saturated sodium bicarbonate in water (250 mL)
  6. extractionThe organic layer was then extracted four times with water (250 mL)
  7. dry with materialThe organic layer was then dried over sodium sulfate (7.5 g)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionTo the black semisolid oil was added acetonitrile (250 mL)
  11. customDuring this time a beige solid precipitated
  12. filtrationwas filtered
  13. customdried under reduced pressure at 40° C. for 16 hours
  14. customA light biege solid was afforded (17 g, 41%)

Sources & evidence

ORD record
ord-f50dc8b210b44e8fa2b4aafa7186899f
Source dataset
uspto-grants-2014_08
Patent number
US08809356B2

Reaction notes

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