Sodium bis(trimethylsilyl)amide → HCID 70984732, compound

HRID 403356Notes

Reaction equation

HRID 403356 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[F:11][C:12]1[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=1[C@@H:19]1[CH2:28][CH2:27][C@@H:26]([OH:29])[C:22]2[N:23]=[CH:24][S:25][C:21]=2[C@H:20]1[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34].N1([C:43]([N:45]2[CH2:50][CH2:49][CH:48]([N:51]3[C:59]4[C:54](=[N:55][CH:56]=[CH:57][CH:58]=4)[NH:53][C:52]3=[O:60])[CH2:47][CH2:46]2)=[O:44])C=CN=C1>CN(C)C=O>[O:60]=[C:52]1[NH:53][C:54]2=[N:55][CH:56]=[CH:57][CH:58]=[C:59]2[N:51]1[CH:48]1[CH2:47][CH2:46][N:45]([C:43]([O:29][C@H:26]2[C:22]3[N:23]=[CH:24][S:25][C:21]=3[C@@H:20]([NH:30][C:31]([O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:37])[C@H:19]([C:13]3[CH:14]=[CH:15][CH:16]=[C:17]([F:18])[C:12]=3[F:11])[CH2:28][CH2:27]2)=[O:44])[CH2:50][CH2:49]1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 584679821-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-oneHCID 71006901HCID 71006901, compound

Product 1

HCID 70984732HCID 70984732, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

NaHMDS (0.228 mL, 0.228 mmol) was added to a dimethylformamide (1 mL) solution of tert-butyl (4R,7S,8S)-7-(2,3-difluorophenyl)-4-hydroxy-5,6,7,8-tetrahydro-4H-cyclohepta[d]thiazol-8-ylcarbamate (20.1 mg, 0.051 mmol) and 1-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (23.7 mg, 0.076 mmol) at 0° C. The reaction was stirred at 0° C. for 1 h and rt for 2 h before quenching with water. The reaction was diluted with ethyl acetate and the organic layer was separated, washed with water and brine and then dried (sodium sulfate), filtered and concentrated. Flash chromatography, eluting with methanol in methylene chloride from 0 to 10% gave the desired product (18.2 mg, 56%): LCMS (M+H=641.38); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.64 (1H, s), 8.07 (1H, d, J=5.0 Hz), 7.31-7.56 (1H, m), 6.93-7.12 (4H, m), 6.22 (1H, d, J=7.5 Hz), 5.24-5.34 (1H, m), 4.96-5.07 (1H, m), 4.32-4.71 (3H, m), 3.61-3.77 (1H, m), 2.88-3.15 (2H, m), 2.29 (4H, d, J=10.5 Hz), 1.83-1.97 (4H, m), 1.30 (9H, s).

Workup

  1. custombefore quenching with water
  2. additionThe reaction was diluted with ethyl acetate
  3. customthe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washFlash chromatography, eluting with methanol in methylene chloride from 0 to 10%

Sources & evidence

ORD record
ord-06900a05ac274a738e9b17e0dbc22431
Source dataset
uspto-grants-2014_06
Patent number
US08748429B2

Reaction notes

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