Triethylamine → HCID 58180965, compound

HRID 1772801Notes

Reaction equation

HRID 1772801 reaction equation
C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[Br:32][C:33]1[CH:34]=[CH:35][C:36]([C:39]([OH:41])=O)=[N:37][CH:38]=1.Cl.[N:43]1([CH2:49][CH:50]([N:54]2[CH:58]=[C:57]([C:59]3[C:60]4[CH:67]=[CH:66][N:65](COCC[Si](C)(C)C)[C:61]=4[N:62]=[CH:63][N:64]=3)[CH:56]=[N:55]2)[CH2:51][C:52]#[N:53])[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1>C1COCC1>[Br:32][C:33]1[CH:34]=[CH:35][C:36]([C:39]([N:46]2[CH2:45][CH2:44][N:43]([CH2:49][CH:50]([N:54]3[CH:58]=[C:57]([C:59]4[C:60]5[CH:67]=[CH:66][NH:65][C:61]=5[N:62]=[CH:63][N:64]=4)[CH:56]=[N:55]3)[CH2:51][C:52]#[N:53])[CH2:48][CH2:47]2)=[O:41])=[N:37][CH:38]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 6085445-Bromopyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)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 58180965HCID 58180965, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (72 uL, 0.52 mol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (39 mg, 0.103 mmol) were added to a solution of 5-bromopyridine-2-carboxylic acid (26 mg, 0.13 mmol) in THF (0.95 mL). After 15 minutes, 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 (51 mg, 0.086 mmol; from Example 12, Step 2) was added and the reaction was stirred for two hours. The reaction was partitioned between ethyl acetate and water. The organic layer was washed successively with water, 0.1 N NaOH and brine, dried over sodium sulfate and concentrated. The residue was dissolved and stirred in a 1:1 mixture of DCM:TFA for 1 hour, concentrated, then stirred in methanol (1 mL) containing ethylenediamine (0.2 mL) for one hour. Preparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH, was used to purify the product (20 mg, 44%). 1H NMR (400 MHz, d6-dmso): δ 12.10 (br s, 1H), 8.81 (s, 1H), 8.70 (dd, 1H), 8.67 (s, 1H), 8.37 (s, 1H), 8.16 (dd, 1H), 7.60 (d, 1H), 7.52 (dd, 1H), 6.97 (d, 1H), 4.98 (tt, 1H), 3.61-3.54 (m, 2H), 3.37-3.28 (m, 2H), 3.24-3.19 (m, 2H), 2.86 (dd, 1H), 2.81 (dd, 1H), 2.63-2.54 (m, 1H), 2.52-2.40 (m, 2H), 2.39-2.31 (m, 1H); LCMS (M+H)+: 520.2/522.2.

Workup

  1. customThe reaction was partitioned between ethyl acetate and water
  2. washThe organic layer was washed successively with water, 0.1 N NaOH and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved
  6. stirringstirred in a 1:1 mixture of DCM
  7. waitTFA for 1 hour
  8. concentrationconcentrated
  9. stirringstirred in methanol (1 mL)
  10. additioncontaining ethylenediamine (0.2 mL) for one hour
  11. washPreparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH
  12. customto purify the product (20 mg, 44%)

Sources & evidence

ORD record
ord-0f9f796f744b4d599112ee749e471d43
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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