Dimethylformamide → HCID 11711768, compound

HRID 2375863Notes

Reaction equation

HRID 2375863 reaction equation
CN(C=O)C.[C:6]([O:10][C:11]([N:13]1[CH2:18][CH:17]=[C:16]([C:19]2[NH:28][C:22]3[N:23]=[CH:24][N:25]=[C:26](Cl)[C:21]=3[CH:20]=2)[CH2:15][CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].CC([O-])(C)C.[K+].[NH2:35][C:36]1[CH:37]=[CH:38][C:39]([C:42]([NH2:44])=[O:43])=[N:40][CH:41]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(Cl)(Cl)Cl>[C:6]([O:10][C:11]([N:13]1[CH2:18][CH:17]=[C:16]([C:19]2[NH:28][C:22]3[N:23]=[CH:24][N:25]=[C:26]([NH:35][C:36]4[CH:41]=[N:40][C:39]([C:42](=[O:43])[NH2:44])=[CH:38][CH:37]=4)[C:21]=3[CH:20]=2)[CH2:15][CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

7

Reactant 4

HCID 6228Dimethylformamide2×HCID 104643925-Aminopyridine-2-carboxamideHCID 23665647Potassium tert-butoxideHCID 58709797tert-butyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 11711768HCID 11711768, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6212ChloroformSolvent

Procedure

Into the DMF (1 mL) solution of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (122 mg, 0.363 mmol) was added t-BuOK (1M in t-BuOH, 0.726 mL, 0.726 mmol) dropwise at RT under N2 over 5 min. The mixture was then put in an ice/water bath and stirred for 10 min. After that time, the DMF (1 mL) solution of 5-aminopyridine-2-carboxylic acid amide (99.5 mg, 0.726 mmol) was added into the above mixture dropwise. The reaction mixture was warmed to RT. Pd2(dba)3.CHCl3 (9.4 mg, 2.5% eq.) and R(+)-BINAP (22.6 mg, 0.1 eq.) were added, and the mixture was heated at 100° C. for 24 h. The mixture was filtered and the filtrate was concentrated in vacuo. The crude was submitted to MS directed purification. A brown oil was obtained that was purified further by HPLC to obtain the title compound as an off-white solid. 1H NMR (DMSO-d6, 400 MHz): δ=1.50 (s, 9H), 2.50 (m, 2H), 3.64 (t, 2H, J=5.6 Hz), 4.12 (brs, 2H), 6.50 (brs, 1H), 6.88 (s, 1H), 7.53 (d, 1H, J=4.2 Hz), 8.04-8.05 (m, 1H), 8.08 (d, 1H, J=8.8 Hz), 8.44 (s, 1H), 8.68 (dd, 1H, J=2.4 & 8.4 Hz), 9.12 (d, 1H, J=2.4 Hz), 9.91 (s, 1H), 12.18 (s, 1H). MS (ES+): m/z 436.10 (100) [MH+]. HPLC: tR=2.75 min (ZQ2000, polar—5 min).

Workup

  1. customThe mixture was then put in an ice/water bath
  2. temperaturethe mixture was heated at 100° C. for 24 h
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate was concentrated in vacuo
  5. custompurification
  6. customA brown oil was obtained
  7. customthat was purified further by HPLC

Sources & evidence

ORD record
ord-2052438ebcc44156abe1c341efdad3d7
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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