Methyl iodide → HCID 118436323, compound

HRID 1775489Notes

Reaction equation

HRID 1775489 reaction equation
CI.[NH2:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2[C:11]3[CH2:24][CH2:23][N:22]([C@@:25]4([CH3:38])[CH2:29][CH2:28][N:27]([C:30](=S)[NH:31][C:32]([CH3:36])([CH3:35])[CH2:33][OH:34])[CH2:26]4)[C:12]=3[N:13]=[C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[N:15]=2)=[CH:6][N:5]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.C(O)C>[CH3:36][C:32]1([CH3:35])[CH2:33][O:34][C:30]([N:27]2[CH2:28][CH2:29][C@@:25]([N:22]3[C:12]4[N:13]=[C:14]([N:16]5[CH2:17][CH2:18][O:19][CH2:20][CH2:21]5)[N:15]=[C:10]([C:7]5[CH:8]=[N:9][C:4]([NH2:3])=[N:5][CH:6]=5)[C:11]=4[CH2:24][CH2:23]3)([CH3:38])[CH2:26]2)=[N:31]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 81531DiisopropylethylamineHCID 118436094HCID 118436094, compound

Product 1

HCID 118436323HCID 118436323, compoundYield 36.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl iodide (15.2 μL, 0.24 mmol) was added to a solution of (S)-3-(4-(2-aminopyrimidin-5-yl)-2-morpholino-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-3-methylpyrrolidine-1-carbothioamide (38.0 mg, 0.074 mmol) and diisopropylethylamine (28.3 μL, 0.16 mmol) in DCM (0.74 mL) and ethanol (0.74 mL) and the mixture was stirred at room temperature for 23 h. The reaction mixture was partitioned between DCM and 50% brine solution. The organic layer was separated, dried with Na2SO4, filtered and concentrated. The residue was purified by preparative SFC (Cosmosil 3-hydroxyphenyl bonded 150×21.2 mm, 5 μm, 100A column) eluting with 15%-50% CO2 in MeOH with a flow rate of 80 mL/min, at 100 bar to give the title compound (12.9 mg, 36%) as a white solid. 1H NMR (700 MHz, DMSO-d6) δ 8.72 (s, 2 H), 6.99 (s, 2 H), 3.94-3.86 (m, 2 H), 3.74 (d, J=10.4 Hz, 1 H), 3.68-3.59 (m, 8H), 3.55-3.52 (m, 1 H), 3.11-3.06 (m, 2 H), 2.41 (dt, J=12.4, 7.9 Hz, 1 H), 2.10 (ddd, J=12.4, 7.3, 5.0 Hz, 1 H), 1.29 (s, 3 H), 1.17-1.10 (m, 6 H). m/z (APCI+) for C24H33N9O2 479.9 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between DCM and 50% brine solution
  2. customThe organic layer was separated
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by preparative SFC (Cosmosil 3-hydroxyphenyl bonded 150×21.2 mm, 5 μm, 100A column)
  7. washeluting with 15%-50% CO2 in MeOH with a flow rate of 80 mL/min, at 100 bar

Sources & evidence

ORD record
ord-d7d158a958ee4dc0a07923976dc433a9
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

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