4-Methylmorpholine → HCID 68781041, compound

HRID 1968532Notes

Reaction equation

HRID 1968532 reaction equation
[Cl:1][C:2]1[C:3]([NH:20][C@@H:21]2[C@@H:26]3[CH2:27][C@@H:23]([CH:24]=[CH:25]3)[C@@H:22]2[C:28]([NH2:30])=[O:29])=[N:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[CH:13]=2)=[N:6][CH:7]=1.[C:31]([NH:34][CH2:35][C:36](O)=[O:37])(=[O:33])[CH3:32].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O.C([O-])(O)=O.[Na+]>[C:31]([NH:34][CH2:35][C:36]([N:17]1[CH2:16][CH2:15][CH:14]([N:12]2[CH:13]=[C:9]([NH:8][C:5]3[N:4]=[C:3]([NH:20][C@@H:21]4[C@@H:26]5[CH2:27][C@@H:23]([CH:24]=[CH:25]5)[C@@H:22]4[C:28]([NH2:30])=[O:29])[C:2]([Cl:1])=[CH:7][N:6]=3)[CH:10]=[N:11]2)[CH2:19][CH2:18]1)=[O:37])(=[O:33])[CH3:32]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10972AcetylglycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68783396HCID 68783396, compound

Product 1

HCID 68781041HCID 68781041, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

(1S,2S,3R,4R)-3-(5-Chloro-2-(1-(piperidin-4-yl)-1H-pyrazol-4-ylamino)pyrimidin-4-ylamino)bicyclo[2.2.1]hept-5-ene-2-carboxamide (85 mg, 0.20 mmol), N-acetylglycine (26 mg, 0.22 mmol), 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (76 mg, 0.40 mmol) and 1-hydroxybenzotriazole hydrate (61 mg, 0.40 mmol) were taken up in N,N-dimethylformamide (1 mL), and N-methylmorpholine (0.11 mL, 1.0 mmol) was added. The reaction mixture was stirred at room temperature for 4 hours, then diluted with NaHCO3 solution (30 mL). The mixture was extracted with ethyl acetate (3×20 mL), and the extracts were dried (Na2SO4) and concentrated. The residue was purified by flash chromatography, using a 12 g silica cartridge and eluting with a gradient from 0 to 8% methanol/CH2Cl2 over 30 minutes at a flow rate of 30 mL/minutes, yielding the desired product. 1H NMR (400 MHz, DMSO-D6) ppm 1.42 (d, J=8.9 Hz, 1H) 1.73-1.86 (m, 2H) 1.88 (s, 3H) 2.01-2.08 (m, 2H) 2.13 (d, J=8.9 Hz, 1H) 2.55 (d, J=7.9 Hz, 1H) 2.76 (s, 1H) 2.87 (s, 1H) 2.93-3.14 (br m, 4H) 3.96 (d, J=5.2 Hz, 2H) 4.17 (t, J=7.9 Hz, 1H) 4.29-4.38 (m, 1H) 6.25 (dd, J=5.8, 3.1 Hz, 1H) 6.34 (dd, J=5.7, 2.9 Hz, 1H) 6.73-7.03 (br, 1H) 7.34-7.52 (br, 1H) 7.47 (d, J=7.6 Hz, 1H) 7.54 (s, 1H) 7.57-7.65 (br s, 1H) 7.75 (s, 1H) 7.84 (s, 1H) 8.69 (s, 1H); MS (ESI(+)) m/e 528 (M+H)+.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  2. dry with materialthe extracts were dried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography
  5. washeluting with a gradient from 0 to 8% methanol/CH2Cl2 over 30 minutes at a flow rate of 30 mL/minutes

Sources & evidence

ORD record
ord-d7ff6707fcc8403688137270a92845ca
Source dataset
uspto-grants-2013_04
Patent number
US08426408B2

Reaction notes

Loading…