Pyridine → HCID 70817985, compound

HRID 82131Notes

Reaction equation

HRID 82131 reaction equation
Cl[C:2](OC1C=CC=CC=1)=[O:3].[CH:11]1([C:14]2[CH:18]=[C:17]([NH2:19])[N:16]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)[N:15]=2)[CH2:13][CH2:12]1.N1C=CC=CC=1.[NH2:32][C:33]1[CH:34]=[C:35]([C:39]([C:41]2[C:49]3[CH:48]=[N:47][CH:46]=[N:45][C:44]=3[N:43]([CH:50]([CH3:52])[CH3:51])[CH:42]=2)=[O:40])[CH:36]=[N:37][CH:38]=1>C1COCC1.CN(C=O)C.C(OCC)(=O)C>[CH:11]1([C:14]2[CH:18]=[C:17]([NH:19][C:2]([NH:32][C:33]3[CH:38]=[N:37][CH:36]=[C:35]([C:39]([C:41]4[C:49]5[CH:48]=[N:47][CH:46]=[N:45][C:44]=5[N:43]([CH:50]([CH3:52])[CH3:51])[CH:42]=4)=[O:40])[CH:34]=3)=[O:3])[N:16]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)[N:15]=2)[CH2:13][CH2:12]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 708172523-Cyclopropyl-1'-methyl-1'H-[1,4']bipyrazolyl-5-ylamineHCID 70817456(5-aminopyridin-3-yl)(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)methanone

Product 1

HCID 70817985HCID 70817985, compoundYield 15%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Phenyl chloroformate (0.03 mL, 0.24 mmol) was added slowly to a solution of 3-Cyclopropyl-1′-methyl-1′H-[1,4′]bipyrazolyl-5-ylamine (Preparation 297, 40 mg, 0.19 mmol) and pyridine (0.03 mL) in THF (2 mL) at 00° C. and the mixture was stirred at room temperature for 4 hours. A solution of (5-Amino-pyridin-3-yl)-(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanone (Preparation 95) (55.4 mg, 0.19 mmol) in DMF (1 mL) and was then added and the reaction mixture heated at 100° C. for 16 hours. The mixture was cooled and diluted with ethyl acetate (15 mL), and washed with aqueous saturated NaHCO3 solution (2×10 mL), water (10 mL), brine (10 mL), dried over sodium sulphate and evaporated to dryness in vacuo. The crude material was purified over preparative TLC plate (eluting with 5% methanol in DCM) to afford the title compound as off white solid in 15% yield, 15 mg. 1H NMR (400 MHz, DMSO-d6) δ: 0.64-0.65 (m, 2H), 0.85-0.88 (m, 2H), 1.56 (d, 6H), 1.82-1.85 (m, 1H), 3.89 (s, 3H), 5.09-5.12 (m, 1H), 6.10 (s, 1H), 7.66 (s, 1H), 8.05 (s, 1H), 8.36 (s, 1H), 8.52 (s, 1H), 8.61 (br s, 1H), 8.65 (s, 1H), 8.78 (s, 1H), 8.99 (s, 1H), 9.45 (s, 2H); LCMS (system 10): Rt=2.75 min; m/z 511 [M+H]+.

Workup

  1. temperaturethe reaction mixture heated at 100° C. for 16 hours
  2. temperatureThe mixture was cooled
  3. washwashed with aqueous saturated NaHCO3 solution (2×10 mL), water (10 mL), brine (10 mL)
  4. dry with materialdried over sodium sulphate
  5. customevaporated to dryness in vacuo
  6. customThe crude material was purified over preparative TLC plate (eluting with 5% methanol in DCM)

Sources & evidence

ORD record
ord-33e8ecca30ff4199be5e6fb71a556a42
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

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