Diisopropylethylamine → HCID 89650297, compound

HRID 2174254Notes

Reaction equation

HRID 2174254 reaction equation
N(C1C=C(NC(=O)NCC)N=CC=1C(O)=O)C1C=CC=CC=1.ClC1N=CC(N)=CN=1.[Cl:31][C:32]1[N:37]=[CH:36][C:35]([NH:38][C:39]([C:41]2[CH:42]=[N:43][C:44]([NH:54][C:55](=[O:59])[NH:56][CH2:57][CH3:58])=[CH:45][C:46]=2[NH:47][C:48]2[CH:49]=[N:50][CH:51]=[CH:52][CH:53]=2)=[O:40])=[CH:34][N:33]=1.Cl.[CH3:61][C:62]1([C:68]([O:70][CH2:71][CH3:72])=[O:69])[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1.C(N(C(C)C)C(C)C)C>CS(C)=O>[Cl:31][C:32]1[N:33]=[CH:34][C:35]([NH:38][C:39]([C:41]2[CH:42]=[N:43][C:44]([NH:54][C:55](=[O:59])[NH:56][CH2:57][CH3:58])=[CH:45][C:46]=2[NH:47][C:48]2[CH:49]=[N:50][CH:51]=[CH:52][CH:53]=2)=[O:40])=[CH:36][N:37]=1.[CH2:57]([NH:56][C:55]([NH:54][C:44]1[N:43]=[CH:42][C:41]([C:39]([NH:38][C:35]2[CH:34]=[N:33][C:32]([N:65]3[CH2:66][CH2:67][C:62]([CH3:61])([C:68]([O:70][CH2:71][CH3:72])=[O:69])[CH2:63][CH2:64]3)=[N:37][CH:36]=2)=[O:40])=[C:46]([NH:47][C:48]2[CH:49]=[N:50][CH:51]=[CH:52][CH:53]=2)[CH:45]=1)=[O:59])[CH3:58]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 122159932-Chloropyrimidin-5-amineHCID 19361804Ethyl 4-methylpiperidine-4-carboxylate hydrochlorideHCID 896500056-(3-Ethylureido)-4-(phenylamino)nicotinic acidHCID 89650805HCID 89650805, compound

Product 2

HCID 89650297HCID 89650297, compoundYield 88%HCID 89650805HCID 89650805, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

N-(2-chloropyrimidin-5-yl)-6-(ethylcarbamoylamino)-4-(3-pyridylamino)pyridine-3-carboxamide (i) was prepared by coupling 4-anilino-6-(ethylcarbamoylamino)pyridine-3-carboxylic acid and 2-chloropyrimidin-5-amine. Compound (i) (30 mg, 73 woe, ethyl 4-methylpiperidine-4-carboxylate hydrochloride (23 mg, 0.11 mmol), N-ethyl-N-isopropyl-propan-2-amine (50 mmol, 0.29 mmol) and DMSO (2 mL) were combined and heated for 2 hr at 80° C. followed by 2 hr at 90° C. The reaction mixture was partitioned between EtOAc (50 mL) and saturated NH4Cl solution (50 mL). The organic layer was separated and further washed with saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL). The organic layer was separated and concentrated to give a crude oil. Flash chromatography on silica, eluting with 0-100% EtOAc gradient in n-heptane, gave crude product. Further flash chromatography (C18 column), eluting with 20-60% acetonitrile gradient in water (containing 0.1% formic acid), afforded Compound 136 (35 mg, 88%). 1H NMR (400 MHz, Acetone) δ 10.24 (s, 1H), 9.56 (s, 1H), 8.74-8.68 (m, 3H), 8.62 (d, J=2.6 Hz, 1H), 8.57 (s, 1H), 8.44 (s, 1H), 8.41 (dd, J=4.7, 1.3 Hz, 1H), 7.79 (ddd, J=8.4, 2.5, 1.5 Hz, 1H), 7.45 (dd, J=8.2, 4.7 Hz, 1H), 7.07 (d, J=4.4 Hz, 1H), 4.36 (dt, J=13.9, 4.4 Hz, 2H), 4.21 (q, J=7.1 Hz, 2H), 3.34-3.26 (m, 4H), 2.16 (s, 2H), 1.51-1.43 (m, 2H), 1.29 (dd, J=9.4, 4.8 Hz, 3H), 1.25 (s, 3H), 1.17 (t, J=7.2 Hz, 3H), [M+H]+ m/z=548.29.

Workup

  1. customThe reaction mixture was partitioned between EtOAc (50 mL) and saturated NH4Cl solution (50 mL)
  2. customThe organic layer was separated
  3. washfurther washed with saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL)
  4. customThe organic layer was separated
  5. concentrationconcentrated
  6. customto give a crude oil
  7. washFlash chromatography on silica, eluting with 0-100% EtOAc gradient in n-heptane
  8. customgave crude product
  9. washFurther flash chromatography (C18 column), eluting with 20-60% acetonitrile gradient in water (containing 0.1% formic acid)

Sources & evidence

ORD record
ord-af888c4cf8a44614a4cfd14cc418b284
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

Loading…