Triethylamine → HCID 86706847, compound

HRID 1507928Notes

Reaction equation

HRID 1507928 reaction equation
CN([P+](O[N:12]1N=[N:19][C:14]2C=CC=C[C:13]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[C:28]([C:31]1[CH:36]=[N:35][N:34]2[CH:37]=[C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH:39]=[C:33]2[C:32]=1[NH:46][C@@H:47]([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[C:48](O)=[O:49])(=[O:30])[NH2:29].NCC#N.C(N(CC)CC)C>CN(C=O)C>[C:13]([CH2:14][NH:19][C:48](=[O:49])[C@@H:47]([NH:46][C:32]1[C:33]2[N:34]([CH:37]=[C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH:39]=2)[N:35]=[CH:36][C:31]=1[C:28]([NH2:29])=[O:30])[C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)#[N:12]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10901AminoacetonitrileHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68291658HCID 68291658, compound

Product 1

HCID 86706847HCID 86706847, compoundYield 63.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

BOP reagent (17.2 mg, 0.039 mmol) was added in one portion to a solution of (S)-2-(3-carbamoyl-6-phenylpyrrolo[1,2-b]pyridazin-4-ylamino)-2-phenylacetic acid (Example 122, 10 mg, 0.026 mmol), 2-aminoacetonitrile (1.82 mg, 0.032 mmol) and triethylamine (0.011 ml, 0.078 mmol) in DMF (0.01 ml). The reaction was allowed to stir at rt for 1 hour before being purified by reverse-phase Prep HPLC (condition A). The fraction containing the major product was concentrated on the rotovap to remove the MeOH and the aqueous slurry of the product was neutralized by addition of ˜1 mL of saturated aq sodium bicarbonate. Sonication of the slurry followed by vacuum filtration and air drying in the funnel afforded the title compound (7 mg, 60% yield). HPLC (condition B): retention time=1.57 min. LCMS (condition B): MH+ m/z 425.2. 1H NMR (500 MHz, MeOD) δ ppm 8.33 (1H, s), 8.07 (1 H, d, J=1.66 Hz), 7.86 (1 H, s), 7.75 (4 H, dd, J=7.63, 2.08 Hz), 7.60 (2H, t, J=7.49 Hz), 7.49-7.57 (3 H, m), 7.41 (1 H, t, J=7.35 Hz), 7.31 (1 H, d, J=1.66 Hz), 6.11 (1 H, s), 4.22-4.44 (1 H, m), 3.17 (2 H, s).

Workup

  1. custombefore being purified by reverse-phase Prep HPLC (condition A)
  2. additionThe fraction containing the major product
  3. concentrationwas concentrated on the rotovap
  4. customto remove the MeOH
  5. additionthe aqueous slurry of the product was neutralized by addition of ˜1 mL of saturated aq sodium bicarbonate
  6. customSonication of the slurry
  7. filtrationfollowed by vacuum filtration and air
  8. customdrying in the funnel

Sources & evidence

ORD record
ord-886fa263fd144398a2b64bca0fca0316
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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