Hydrochloric Acid → imino-methyl-[1-[6-[(3R)-3-methylmorpholin-4-yl]-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl]cyclopropyl]-oxo-lambda6-sulfane

HRID 1749061Notes

Reaction equation

HRID 1749061 reaction equation
[OH-].[Na+].[CH3:3][C@@H:4]1[CH2:9][O:8][CH2:7][CH2:6][N:5]1[C:10]1[CH:15]=[C:14]([C:16]2([S:19]([CH3:22])(=[NH:21])=[O:20])[CH2:18][CH2:17]2)[N:13]=[C:12]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]3[N:29](S(C4C=CC(C)=CC=4)(=O)=O)[CH:30]=[CH:31][C:24]=23)[N:11]=1.O.Cl>COCCOC>[CH3:3][C@@H:4]1[CH2:9][O:8][CH2:7][CH2:6][N:5]1[C:10]1[CH:15]=[C:14]([C:16]2([S:19]([CH3:22])(=[NH:21])=[O:20])[CH2:18][CH2:17]2)[N:13]=[C:12]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]3[NH:29][CH:30]=[CH:31][C:24]=23)[N:11]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium Hydroxide2×HCID 86660216(3R)-3-methyl-4-(6-(1-(S-methylsulfonimidoyl)cyclopropyl)-2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)morpholine

Product 1

HCID 86660217imino-methyl-[1-[6-[(3R)-3-methylmorpholin-4-yl]-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl]cyclopropyl]-oxo-lambda6-sulfaneYield 52%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
50 °C

Procedure

Sodium hydroxide, 2M aqueous solution (9.95 ml, 19.90 mmol) was added to (3R)-3-methyl-4-(6-(1-(S-methylsulfonimidoyl)cyclopropyl)-2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)morpholine (6.44 g, 11.37 mmol) in DME (100 ml)/water (25.00 ml). The resulting solution was stirred at 50° C. for 18 hours. Further NaOH, 2M aqueous solution (18 ml, 36.00 mmol) was added and the mixture was stirred at 50° C. for a further 3 days. The reaction mixture was acidified with 2M HCl (˜22 ml) to pH5. The reaction mixture was evaporated and the residue was dissolved in DCM (250 ml) and washed with water (200 ml). The organic layer was dried over MgSO4, filtered and then evaporated to approximately 50 ml in volume. The solution was purified by flash chromatography on silica, eluting with a gradient of 0 to 7% MeOH in DCM. Pure fractions were evaporated to afford 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-(S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (2.440 g, 52%); 1H NMR (400 MHz, DMSO-d6) 1.27 (3H, d), 1.42 (1H, dd), 1.47-1.58 (2H, m), 1.68-1.80 (1H, m), 3.10 (3H, s), 3.24-3.31 (1H, m), 3.51 (1H, t), 3.66 (1H, dd), 3.80 (1H, d), 3.83-3.88 (1H, m), 4.00 (1H, dd), 4.20 (1H, s), 4.57 (1H, s), 6.99 (1H, d), 7.22 (1H, dd), 7.53-7.63 (1H, m), 7.94 (1H, d), 8.34 (1H, t), 11.80 (1H, s); m/z: (ES+) MH+, 413.47.

Workup

  1. stirringthe mixture was stirred at 50° C. for a further 3 days
  2. customThe reaction mixture was evaporated
  3. dissolutionthe residue was dissolved in DCM (250 ml)
  4. washwashed with water (200 ml)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated to approximately 50 ml in volume
  8. customThe solution was purified by flash chromatography on silica
  9. washeluting with a gradient of 0 to 7% MeOH in DCM
  10. customPure fractions were evaporated

Sources & evidence

ORD record
ord-6d7b30e7c45e43fdac6e42677f98eec6
Source dataset
uspto-grants-2015_10
Patent number
US09155742B2

Reaction notes

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