Acetonitrile → HCID 58180877, compound

HRID 1772799Notes

Reaction equation

HRID 1772799 reaction equation
Cl.[N:2]1([CH2:8][CH:9]([N:13]2[CH:17]=[C:16]([C:18]3[C:19]4[CH:26]=[CH:25][N:24](COCC[Si](C)(C)C)[C:20]=4[N:21]=[CH:22][N:23]=3)[CH:15]=[N:14]2)[CH2:10][C:11]#[N:12])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(N(CC)CC)C.[F:42][C:43]1[CH:44]=[C:45]([CH:49]=[CH:50][C:51]=1[O:52][CH3:53])[C:46](Cl)=[O:47].C(#N)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[F:42][C:43]1[CH:44]=[C:45]([CH:49]=[CH:50][C:51]=1[O:52][CH3:53])[C:46]([N:5]1[CH2:4][CH2:3][N:2]([CH2:8][CH:9]([N:13]2[CH:17]=[C:16]([C:18]3[C:19]4[CH:26]=[CH:25][NH:24][C:20]=4[N:21]=[CH:22][N:23]=3)[CH:15]=[N:14]2)[CH2:10][C:11]#[N:12])[CH2:7][CH2:6]1)=[O:47]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 27792553-Fluoro-4-methoxybenzoyl chloride2×HCID 670549114-piperazin-1-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloride

Product 1

HCID 58180877HCID 58180877, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-piperazin-1-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloride (125 mg, 0.211 mmol; from Example 12, Step 2) in DCM (2 mL) was added triethylamine (177 uL, 1.27 mmol) followed by 3-fluoro-4-methoxybenzoyl chloride (80 mg, 0.4 mmol). The reaction was stirred at for 16 hours. 4-Dimethylaminopyridine (5 mg, 0.04 mmol) was added. Acetonitrile (0.30 mL) was added to aid in solubility and additional 3-fluoro-4-methoxybenzoyl chloride (80 mg, 0.4 mmol) was added. When reaction was complete as evidenced by LCMS, solvent was removed in vacuo. The residue was stirred in a mixture of 1:1 DCM:TFA for 1 hour, concentrated, then stirred in MeOH (3 mL) containing ethylenediamine (0.5 mL). Preparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH, was used to purify the product (50 mg, 48%). 1H NMR (400 MHz, d6-dmso): δ 12.12 (br s, 1H), 8.81 (s, 1H), 8.68 (s, 1H), 8.37 (s, 1H), 7.60 (d, 1H), 7.27-7.15 (m, 3H), 6.98 (d, 1H), 4.99 (tt, 1H), 3.86 (s, 3H), 3.57-3.17 (m, 6H), 2.89-2.77 (m, 2H), 2.60-2.32 (m, 4H); LCMS (M+H)+: 489.1.

Workup

  1. additionwas added
  2. customWhen reaction
  3. customwas removed in vacuo
  4. stirringThe residue was stirred in a mixture of 1:1 DCM
  5. waitTFA for 1 hour
  6. concentrationconcentrated
  7. stirringstirred in MeOH (3 mL)
  8. additioncontaining ethylenediamine (0.5 mL)
  9. washPreparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH
  10. customto purify the product (50 mg, 48%)

Sources & evidence

ORD record
ord-afdc70c5399840a7aec3d9c952a5d228
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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