Dimethylamine → 2-chloro-7-cycloheptyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

HRID 627320Notes

Reaction equation

HRID 627320 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:10]=[C:9]([CH2:11][OH:12])[N:8]([CH:13]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[C:6]=2[N:7]=1.[CH3:20][NH:21][CH3:22].C1COCC1.[C-]#N.[Na+]>CN(C=O)C.[O-2].[O-2].[Mn+4]>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:10]=[C:9]([C:11]([N:21]([CH3:22])[CH3:20])=[O:12])[N:8]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]3)[C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 8929Sodium CyanideHCID 86686625(2-chloro-7-cycloheptyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)methanol

Product 1

HCID 866866262-chloro-7-cycloheptyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamideYield 85%

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of (2-chloro-7-cycloheptyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)methanol (6.24 g, 22.3 mmol) in DMF (100 mL) were added a solution of dimethylamine in THF (2 M, 46 mL, 4.1 equiv) and sodium cyanide (1.04 g, 0.95 equiv) and the resulting mixture was stirred at room temperature for 4 min. The reaction mixture was treated with manganese dioxide (100.4 g, 45 equiv) in four portions over 1 h and stirred for additional 1 h. The reaction mixture was filtered through a pad of Celite (rinsed with EtOAc 600 mL). The filtrate was washed with water (200 mL). The aqueous phase was extracted with EtOAc (2×150 mL). Combined organics were washed with 4% aqueous solution of NaCl (2×250 mL), dried over Na2SO4, filtered and concentrated in vacuo. Trituration of the residue in MeCN followed by column chromatography of the mother liquor (EtOAc/Heptane 30 to 100%) provided 2-chloro-7-cycloheptyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (6.07 g) in 85% yield. 1H NMR (400 MHz, CDCl3) δ 8.81 (s, 1H), 6.52 (s, 1H), 4.63 (tt, J=11, 4.0 Hz, 1H), 3.20 (s, 3H), 3.11 (s, 3H), 2.52 (m, 2H), 1.99 (m, 2H), 1.88 (m, 2H), 1.70 (m, 4H), 1.58 (m, 2H) MS m/z 321.5 (M+H)+

Workup

  1. stirringstirred for additional 1 h
  2. filtrationThe reaction mixture was filtered through a pad of Celite (rinsed with EtOAc 600 mL)
  3. washThe filtrate was washed with water (200 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (2×150 mL)
  5. washCombined organics were washed with 4% aqueous solution of NaCl (2×250 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f071a5e35e0b486ab72b57158e1fc2a9
Source dataset
uspto-grants-2016_04
Patent number
US09309252B2

Reaction notes

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