4-Methylmorpholine → ethyl 2-(6-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)hexanamido)acetate

HRID 20713Notes

Reaction equation

HRID 20713 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:55])[C:31]=1[NH:32][C:33]1[C:42]2[C:37](=[C:38]([O:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][C:51](O)=[O:52])[C:39]([O:43][CH3:44])=[CH:40][CH:41]=2)[O:36][C:35](=[O:54])[CH:34]=1.CN1CCOCC1.[NH2:63][CH2:64][C:65]([O:67][CH2:68][CH3:69])=[O:66].Cl.OP([O-])(O)=O.[K+]>CN(C=O)C>[Cl:25][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([Cl:55])[C:31]=1[NH:32][C:33]1[C:42]2[C:37](=[C:38]([O:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][C:51]([NH:63][CH2:64][C:65]([O:67][CH2:68][CH3:69])=[O:66])=[O:52])[C:39]([O:43][CH3:44])=[CH:40][CH:41]=2)[O:36][C:35](=[O:54])[CH:34]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 516951Monobasic potassium phosphateHCID 2723640Glycine ethyl ester, hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 248497096-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)hexanoic acid

Product 1

HCID 24849342ethyl 2-(6-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)hexanamido)acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (180 mg, 0.47 mmol) was added to a solution of 6-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)hexanoic acid (187 mg, 0.4 mmol, Example 44), 4-methylmorpholine (0.2 mL, 1.8 mmol), and DMF (2 mL). After 5 min, this solution was added to Gly-OEt•HCl (65 mg, 0.47 mmol). After 75 min, the reaction was poured into 1M KH2PO4 (30 mL) and extracted with ethyl acetate (40 mL×2). The combined extracts were dried, filtered, concentrated, and purified by silica gel chromatography (1:4→0:1; hexanes:ethyl acetate) to give ethyl 2-(6-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)hexanamido)acetate: 1H NMR (400 MHz, DMSO-d6): δ 9.51 (s, 1H), 8.81 (s, 2H), 8.21 (t, 1H), 7.94 (d, 1H), 7.20 (d, 1H), 4.63 (s, 1H), 4.05 (q, 2H), 3.97 (t, 2H), 3.92 (s, 3H), 3.77 (d, 2H), 2.14 (t, 2H), 1.68 (m, 2H), 1.55 (m, 2H), 1.44 (m, 2H), 1.16 (t, 3H); MS (ESI): 552.0.

Workup

  1. waitAfter 75 min
  2. extractionextracted with ethyl acetate (40 mL×2)
  3. customThe combined extracts were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (1:4→0:1; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-46668affb9dc4a02aeb91bb5a8fd63ab
Source dataset
uspto-grants-2010_06
Patent number
US07745646B2

Reaction notes

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