Lithium Hexamethyldisilazide → HCID 67130988, compound

HRID 1678685Notes

Reaction equation

HRID 1678685 reaction equation
C[O:2][C:3](=O)[CH:4]([C:11]1[N:12]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)[N:13]=[C:14]2[C:19]=1[CH2:18][CH2:17][CH2:16][CH2:15]2)[CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH2:38][C:39]1[CH:46]=[CH:45][C:42]([C:43]#[N:44])=[CH:41][C:40]=1[F:47]>C1COCC1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([N:12]2[C:11]([CH:4]([CH:5]3[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]3)[C:3]([NH:38][C:39]3[CH:46]=[CH:45][C:42]([C:43]#[N:44])=[CH:41][C:40]=3[F:47])=[O:2])=[C:19]3[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]3)=[N:13]2)=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27564314-Amino-3-fluorobenzonitrileHCID 67131114HCID 67131114, compound

Product 1

HCID 67130988HCID 67130988, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of [rac]-[2-(4-chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-cyclohexyl-acetic acid methyl ester (250 mg, 0.64 mmol) in dry THF was added LiHMDS (1.0 M solution in THF; 4.5 ml, 4.5 mmol) at −30° C. and stirring continued for another 30 min at that temperature. 4-Amino-3-fluoro-benzonitrile (90.64 mg, 0.768 mmol; CAS Reg. No. 115661-37-5) in THF (1 ml) was then added at that temperature and slowly brought to room temperature. Reaction mixture was then stirred at room temperature for 13 h. TLC shows formation of a new spot. LC-MS of the crude material shows formation of desired product. Reaction mixture was quenched with saturated NH4Cl and the aqueous layer was extracted with EtOAc (3×5 ml). Combined organic layers were washed with brine and concentrated under reduced pressure to give crude material (260 mg); which was then purified by column chromatography [SiO2 (230-400 mesh), EtOAc:hexane 30:70] to give the title compound (130 mg, 42%) as light yellow solid.

Workup

  1. customslowly brought to room temperature
  2. customReaction mixture
  3. stirringwas then stirred at room temperature for 13 h

Sources & evidence

ORD record
ord-024f2011c70c4f948e36972700901e36
Source dataset
uspto-grants-2011_08
Patent number
US08008505B2

Reaction notes

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