Hydrochloric Acid → HCID 59333963, compound

HRID 1927007Notes

Reaction equation

HRID 1927007 reaction equation
Cl.[CH2:2]([NH:4][C:5]1[N:10]=[C:9]([NH:11][C:12]2[C:13]3[CH2:24][NH:23][C:22]([CH3:26])([CH3:25])[C:14]=3[N:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[N:16]=2)[C:8]([F:27])=[CH:7][N:6]=1)[CH3:3].CCN(C(C)C)C(C)C.[Cl:37][C:38](Cl)([O:40]C(=O)OC(Cl)(Cl)Cl)Cl>O1CCOCC1.C(Cl)Cl>[Cl:37][C:38]([N:23]1[CH2:24][C:13]2[C:12]([NH:11][C:9]3[C:8]([F:27])=[CH:7][N:6]=[C:5]([NH:4][CH2:2][CH3:3])[N:10]=3)=[N:16][N:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:14]=2[C:22]1([CH3:25])[CH3:26])=[O:40]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 59333974HCID 59333974, compound

Product 1

HCID 59333963HCID 59333963, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a suspension of B1(iv) (4.43 g, 9.6 mmol) in dioxane (25 mL) was added HCl (20 mL, 4M in dioxane). The reaction was stirred at room temperature for 2 h then concentrated. To a solution of the HCl salt of ethyl 3-{[2-(ethylamino)-5-fluoropyrimidin-4-yl]amino}-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate (1.27 g, 2.7 mmol) in CH2Cl2 (40 mL) was added DIPEA (1.57 g, 12.1). The reaction was cooled to −78° C. and triphosgene (0.48 g, 0.6 mmol) was added in a solution of CH2Cl2 (10 mL) with an addition funnel over 15 min. The reaction was quenched at −78° C. with water then warmed to room temperature. The mixture was made to pH 8-9 with NaHCO3 and extracted with CH2Cl2 (2×15 mL). The combined extracts were washed with brine (15 mL) then dried, filtered and concentrated. The crude material was purified by silica gel column chromatography using 0-3% 7N NH3/MeOH in CH2Cl2 to give the desired compound B1(v) as a white foam (489 mg, 36%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.07 (t, J=7.2 Hz, 3H), 1.33 (t, J=7.2 Hz, 3H), 1.78-1.84 (m, 6H), 3.12-3.28 (m, 2H), 4.42 (q, J=7.2 Hz, 2H), 4.78 (s, 2H), 6.69-6.97 (m, 1H), 7.77-8.08 (m, 1H), 10.41 (s, 1H). Mass spectrum: Calcd for C17H22ClFN7O3 (M+H): 426. Found 426.

Workup

  1. concentrationthen concentrated
  2. temperatureThe reaction was cooled to −78° C.
  3. customThe reaction was quenched at −78° C. with water
  4. temperaturethen warmed to room temperature
  5. extractionextracted with CH2Cl2 (2×15 mL)
  6. washThe combined extracts were washed with brine (15 mL)
  7. customthen dried
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-fa4bbfa67ed7454b9a620d64f2870ddf
Source dataset
uspto-grants-2012_05
Patent number
US08183255B2

Reaction notes

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