Hydrochloric Acid → HCID 118436034, compound

HRID 1775482Notes

Reaction equation

HRID 1775482 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9]3[CH2:23][CH2:22][N:21]([C@@:24]4([CH3:42])[CH2:28][CH2:27][N:26]([C:29](=[O:41])[C:30]([NH:33]C(=O)OC(C)(C)C)([CH3:32])[CH3:31])[CH2:25]4)[C:10]=3[N:11]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH3:20])[N:13]=2)=[CH:4][N:3]=1.Cl.O1CCOCC1.C1(C)C=CC=CC=1>CO>[NH2:33][C:30]([CH3:31])([CH3:32])[C:29]([N:26]1[CH2:27][CH2:28][C@@:24]([N:21]2[C:10]3[N:11]=[C:12]([N:14]4[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]4[CH3:20])[N:13]=[C:8]([C:5]4[CH:4]=[N:3][C:2]([NH2:1])=[N:7][CH:6]=4)[C:9]=3[CH2:23][CH2:22]2)([CH3:42])[CH2:25]1)=[O:41]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 312751,4-DioxaneHCID 118447905HCID 118447905, compound

Product 1

HCID 118436034HCID 118436034, compoundYield 971.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of tert-butyl {1-[(3S)-3-{4-(2-aminopyrimidin-5-yl)-2[(3S)-3-methylmorpholin-4-yl]-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-3-methylpyrrolidin-1-yl]-2-methyl-1-oxopropan-2-yl}carbamate (778 mg, 0.1 mmol) in MeOH (6.5 mL) was added 4 N HCl in dioxane (6.7 mL, 26.8 mmol) dropwise at 0° C. and the reaction was stirred at room temperature for 2 h. Toluene was added and the mixture was concentrated to give a residue that was purified by SFC/ZymorSpher HAP column (150×21.2 mm) eluting with 15-35% CO2 in MeOH over 6 min at 120 bar and with a flow of 100 mL/min to give 468 mg of the title compound as a white solid. The solid was treated with hydroxide resin in MeOH for 15 min or until pH˜8 was reached. The resin was removed by filtration washing with MeOH and 7 N ammonia in MeOH several times. The filtrate was concentrated under reduced pressure, dried under high vacuum and lyophilized to give the title compound (387.8 mg, 60%) as a white solid. 1H NMR (400 MHz, DMSO-d6, 80° C.) δ 8.73 (s, 2 H), 6.60 (br s, 2 H), 4.63 (d, J=6.6 Hz, 1 H), 4.36-4.16 (m, 2 H), 4.00 (d, J=11.6 Hz, 1 H), 3.94-3.85 (m, 1 H), 3.75-3.37 (m, 7 H), 3.22-3.05 (m, 3 H), 2.44-2.29 (m, 1 H), 2.08-1.95 (m, 1 H), 1.69 (br s, 2 H), 1.32 (s, 3 H), 1.28 (s, 6 H), 1.22 (d, J=6.72 Hz, 3 H). m/z (APCI+) for C24H35N9O2 482.6 (M+H)+.

Workup

  1. concentrationthe mixture was concentrated
  2. customto give a residue that
  3. customwas purified by SFC/ZymorSpher HAP column (150×21.2 mm)
  4. washeluting with 15-35% CO2 in MeOH over 6 min at 120 bar and with a flow of 100 mL/min

Sources & evidence

ORD record
ord-6cc21d05eaa049129a2b17b3a2b306be
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

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