Oxamic Acid → HCID 68291415, compound

HRID 877732Notes

Reaction equation

HRID 877732 reaction equation
OC(C(F)(F)F)=O.[CH3:8][C:9]1([CH3:36])[C@H:14]([NH:15][C:16]2[C:17]3[N:18]([CH:25]=[C:26]([C:28]4[CH:29]=[N:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=4)[CH:27]=3)[N:19]=[CH:20][C:21]=2[C:22]([NH2:24])=[O:23])[CH2:13][CH2:12][NH:11][CH2:10]1.[NH2:37][C:38](=[O:42])[C:39](O)=[O:40].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[NH2:37][C:38](=[O:42])[C:39]([N:11]1[CH2:12][CH2:13][C@@H:14]([NH:15][C:16]2[C:17]3[N:18]([CH:25]=[C:26]([C:28]4[CH:29]=[N:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=4)[CH:27]=3)[N:19]=[CH:20][C:21]=2[C:22]([NH2:24])=[O:23])[C:9]([CH3:36])([CH3:8])[CH2:10]1)=[O:40]

Participants

6

Reactant 4

HCID 974Oxamic AcidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86707897HCID 86707897, compound

Product 1

HCID 68291415HCID 68291415, compoundYield 38.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To solution of (R)-4-(3,3-dimethylpiperidin-4-ylamino)-6-(6-methoxypyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide TFA salt (20 mg, 0.039 mmol), 2-amino-2-oxoacetic acid (4.20 mg, 0.047 mmol) and HATU (22.43 mg, 0.059 mmol) in DMF (0.3 mL) was added triethylamine (0.022 mL, 0.157 mmol) and the resulting mixture was stirred at rt overnight. The mixture was quenched with 0.3 mL of MeOH, diluted with MeOH, filtered and was purified via preparative reverse phase HPLC. The fraction containing the major product was concentrated under vacuum to afford the title compound as a tan solid (10 mg, 0.015 mmol, 38%). HPLC (Method B) retention time=2.88 min. LCMS (m+1)=466.3. 1H NMR (400 MHz, METHANOL-d4) δ 8.59 (t, J=2.2 Hz, 1H), 8.24 (dt, J=8.7, 2.8 Hz, 1H), 8.21 (s, 1H), 8.03 (t, J=2.0 Hz, 1H), 7.31 (dd, J=5.7, 1.8 Hz, 1H), 7.05 (dd, J=8.5, 2.3 Hz, 1H), 4.46-4.30 (m, 2H), 4.07-4.00 (m, 4H), 3.78 (dd, J=13.8, 1.7 Hz, 1H), 3.68-3.51 (m, 1H), 3.21-3.08 (m, 1H), 2.23 (dt, J=13.6, 4.0 Hz, 1H), 2.04-1.75 (m, 1H), 1.22-1.06 (m, 6H).

Workup

  1. customThe mixture was quenched with 0.3 mL of MeOH
  2. additiondiluted with MeOH
  3. filtrationfiltered
  4. customwas purified via preparative reverse phase HPLC
  5. additionThe fraction containing the major product
  6. concentrationwas concentrated under vacuum

Sources & evidence

ORD record
ord-9f4deb50f5e14ca88924d6048a02f9c3
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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