Triethylsilane → N-cyclopropyl-2,4-difluoro-5-((2-(pyridin-2-ylamino)thiazol-5-yl)methylamino)benzamide

HRID 1985760Notes

Reaction equation

HRID 1985760 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[S:9][C:10]([CH:13]=O)=[CH:11][N:12]=1.[NH2:15][C:16]1[C:17]([F:29])=[CH:18][C:19]([F:28])=[C:20]([CH:27]=1)[C:21]([NH:23][CH:24]1[CH2:26][CH2:25]1)=[O:22].C([SiH](CC)CC)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH:24]1([NH:23][C:21](=[O:22])[C:20]2[CH:27]=[C:16]([NH:15][CH2:13][C:10]3[S:9][C:8]([NH:7][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)=[N:12][CH:11]=3)[C:17]([F:29])=[CH:18][C:19]=2[F:28])[CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 12052TriethylsilaneHCID 219665075-amino-N-cyclopropyl-2,4-difluorobenzamideHCID 220190582-(Pyridin-2-ylamino)thiazole-5-carbaldehyde

Product 1

HCID 11632737N-cyclopropyl-2,4-difluoro-5-((2-(pyridin-2-ylamino)thiazol-5-yl)methylamino)benzamideYield 47.3%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A mixture of 2-[pyridin-2-ylamino]-thiazole-5-carbaldehyde (41.0 mg, 0.2 mmol) and 5-amino-N-cyclopropyl-2,4-difluorobenzamide (46.6 mg, 0.22 mmol) in TFA/DCM (1:1, 1 mL) was stirred at RT for 10 min and triethylsilane (0.1 mL) was added. The mixture was stirred for 1 h, then concentrated and the residue was neutralized with NaHCO3 solution and the precipitates occurred. The precipitates were collected, washed with water and dried. The solid was triturated with MeOH and filtered to afford the title compound as a grayish solid (38 mg, 47%). Small amount of solid was boiled in methanol, the mixture was cooled to RT and filtered to afford a white solid. MS m/z 402 (M+H)+. 1H NMR (DMSO-d6) δ 8.23 (d, 1H, J=4.0 Hz), 8.15 (s, 1H), 7.65 (t, 1H, J=7.15 Hz), 7.26 (s, 1H), 7.16 (m, 1H), 7.01 (d, 1H, J=8.75 Hz), 6.95 (m, 1H), 6.89 (t, 1H, J=7.15 Hz), 6.12 (s 1H), 4.43 (m, 2H), 2.79 (m, 1H), 0.69 (m, 2H), 0.51 (m, 2H).

Workup

  1. stirringThe mixture was stirred for 1 h
  2. concentrationconcentrated
  3. customThe precipitates were collected
  4. washwashed with water
  5. customdried
  6. customThe solid was triturated with MeOH
  7. filtrationfiltered

Sources & evidence

ORD record
ord-3b6b829496bf4137b59f671f50cbdd6d
Source dataset
uspto-grants-2009_06
Patent number
US07547711B2

Reaction notes

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