Acetone → HCID 58486353, compound

HRID 1466360Notes

Reaction equation

HRID 1466360 reaction equation
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][C:14](=[O:19])[C@:13]12[CH2:21][C@H:20]1[C:22]1[CH:30]=[C:29]2[C:25]([C:26]([C:31]3[CH:36]=[CH:35][C:34]([N:37]4[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]4)=[CH:33][CH:32]=3)=[N:27][NH:28]2)=[CH:24][CH:23]=1.[CH3:43][C:44]([CH3:46])=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.CO.CCOCC>[CH:44]([N:40]1[CH2:41][CH2:42][N:37]([C:34]2[CH:33]=[CH:32][C:31]([C:26]3[C:25]4[C:29](=[CH:30][C:22]([C@H:20]5[C@@:13]6([C:12]7[C:16](=[CH:17][CH:18]=[C:10]([O:9][CH3:8])[CH:11]=7)[NH:15][C:14]6=[O:19])[CH2:21]5)=[CH:23][CH:24]=4)[NH:28][N:27]=3)=[CH:36][CH:35]=2)[CH2:38][CH2:39]1)([CH3:46])[CH3:43]

Participants

7

Reactant 3

HCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 67448475HCID 67448475, compound

Product 1

HCID 58486353HCID 58486353, compoundYield 46%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
40 °C

Procedure

A solution of (1R*,2S*)-5′-methoxy-2-(3-(4-(piperazin-1-yl)phenyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-one 2,2,2-trifluoroacetate (30 mg, 0.052 mmol) in 1,2-dichloroethane (0.5 mL), MeOH (0.1 mL) was treated with acetone (80 uL, 1.04 mmol) and NaBH(OAc)3 (17 mg, 0.078 mmol) and the reaction was heated to 40° C. for 18 h. The solvent was removed and the residue purified by column chromatography (silica gel, CH2Cl2/MeOH/7N NH3 in MeOH, 96:3:1) which gave an impure solid that was sonicated in Et2O. The solvent was decanted off and the solid dried to give the title product as an off-white powder (12 mg, 46%); 1H NMR (400 MHz, DMSO-d6) δ 12.99 (s, 1H), 10.44 (s, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.81 (d, J=8.4 Hz, 2H), 7.47 (s, 1H), 7.06-6.99 (m, 3H), 6.74 (d, J=8.5 Hz, 1H), 6.57 (d, J=7.5 Hz, 1H), 5.69 (s, 1H), 3.29 (s, 3H), 3.25-3.15 (m, 4H), 2.67 (m, 2H), 2.65-2.55 (m, 4H), 2.35-2.32 (m, 1H), 2.22-1.98 (m, 1H), 1.01 (d, J=5.6 Hz, 6H); MS ESI [M+H]+ 508.3, calcd for [C31H33N5O2+H]+ 508.27.

Workup

  1. customThe solvent was removed
  2. customthe residue purified by column chromatography (silica gel, CH2Cl2/MeOH/7N NH3 in MeOH, 96:3:1) which
  3. customgave an impure solid
  4. customThe solvent was decanted off
  5. customthe solid dried

Sources & evidence

ORD record
ord-31c98842564146d08b6c7e7f3310f811
Source dataset
uspto-grants-2015_04
Patent number
US08999968B2

Reaction notes

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