Dichloromethane → HCID 68261105, compound

HRID 627443Notes

Reaction equation

HRID 627443 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([N:22]5[C:29](=[O:30])[CH2:28][C@@H:27]6[NH:31][C@@H:24]([CH2:25][CH2:26]6)[CH2:23]5)=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:37][S:38](Cl)(=[O:40])=[O:39].C(N(C(C)C)CC)(C)C.C(Cl)Cl>CCOC(C)=O>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([N:22]5[C:29](=[O:30])[CH2:28][C@@H:27]6[N:31]([S:38]([CH3:37])(=[O:40])=[O:39])[C@@H:24]([CH2:25][CH2:26]6)[CH2:23]5)=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 53377611HCID 53377611, compound

Product 1

HCID 68261105HCID 68261105, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A sample of 7-Cyclopentyl-N,N-dimethyl-2-(5-((1S,6R)-4-oxo-3,9-diazabicyclo[4.2.1]nonan-3-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (50 mg, 0.102 mmol), methanesulfonyl chloride (12.3 mg, 0.107 mmol) and diisopropyl ethylamine (0.027 ml, 0.154 mmol) were combined into 1 ml DCM in a crew cap vial along with a stir bar and allowed to stir for 16 hr. The reaction was then taken up into EtOAc, and extracted with saturated Na2CO3 solution, then with brine and the organic layer dried over Na2SO4. The crude product was purified by normal phase chromatography (0-75% ethyl acetate in Heptane) which gave 7-cyclopentyl-N,N-dimethyl-2-(5-((1S,6R)-9-(methylsulfonyl)-4-oxo-3,9-diazabicyclo[4.2.1]nonan-3-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (25 mg) in 44% yield. 1H NMR (400 MHz, CDCl3) δ ppm 8.66 (s, 2H), 8.47 (d, J=9.09 Hz, 2H), 8.07 (d, J=2.53 Hz, 1H), 7.46 (m, 1H), 6.40 (s, 1H), 4.73 (m, 1H), 4.42 (m, 1H), 4.31 (m, 1H), 4.20 (d, 1H), 3.64 (s, 2H), 3.09 (s, 6H), 3.00 (d, J=4.04 Hz, 1H), 2.90 (s, 3H), 2.49 (m, 2H), 2.00 (m, 4H), 1.66 (br. s., 4H). MS m/z 566.9 (M+H).

Workup

  1. customcap vial along with a stir bar
  2. extractionextracted with saturated Na2CO3 solution
  3. dry with materialwith brine and the organic layer dried over Na2SO4
  4. customThe crude product was purified by normal phase chromatography (0-75% ethyl acetate in Heptane) which

Sources & evidence

ORD record
ord-251dbe8cc5f84e10981d233f487fdbc1
Source dataset
uspto-grants-2016_04
Patent number
US09309252B2

Reaction notes

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