Bis(cyclohexylmethyl)amine → HCID 44469127, compound

HRID 1615857Notes

Reaction equation

HRID 1615857 reaction equation
[CH2:1]([N:4]1[C:13](=[O:14])[C:8]2([CH2:12][CH2:11][CH2:10][CH2:9]2)[NH:7][CH2:6][C@:5]1([C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=1)[CH3:15])[CH:2]=[CH2:3].Br[C:25]1[CH:42]=[C:41]2[C:28]([CH2:29][C@@:30]3([CH2:40]2)[C:38]2[C:33](=[N:34][CH:35]=[CH:36][CH:37]=2)[NH:32][C:31]3=[O:39])=[CH:27][C:26]=1[C:43]#[N:44].C1(CNCC2CCCCC2)CCCCC1>CC(N(C)C)=O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:22][C:20]1[CH:21]=[C:16]([C@@:5]2([CH3:15])[N:4]([CH2:1]/[CH:2]=[CH:3]/[C:25]3[CH:42]=[C:41]4[C:28]([CH2:29][C@@:30]5([CH2:40]4)[C:38]4[C:33](=[N:34][CH:35]=[CH:36][CH:37]=4)[NH:32][C:31]5=[O:39])=[CH:27][C:26]=3[C:43]#[N:44])[C:13](=[O:14])[C:8]3([CH2:12][CH2:11][CH2:10][CH2:9]3)[NH:7][CH2:6]2)[CH:17]=[C:18]([F:23])[CH:19]=1

Participants

6

Reactant 3

HCID 4594378Bis(cyclohexylmethyl)amineHCID 58118672HCID 58118672, compoundHCID 66864394HCID 66864394, compound2×

Product 1

HCID 44469127HCID 44469127, compound

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of (8R)-9-allyl-8-(3,5-difluorophenyl)-8-methyl-6,9-diazaspiro[4.5]decan-10-one (84 mg, 0.262 mmol), (2R)-6-bromo-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-5-carbonitrile (98 mg, 0.288 mmol, described in Intermediate 26) and N,N-dicyclohexylmethylamine (0.0612 mL, 0.288 mmol) in degassed DMA (1.7 mL) at ambient temperature was added bis(tri-t-butylphosphine)palladium (44.2 mg, 0.087 mmol). The reaction mixture was heated at 120° C. for 18 h, cooled, and filtered through a plug of Celite, washing with EtOAc. The filtrate was concentrated in vacuo and the residue was first purified by HPLC using reverse phase C18 column, eluting with a gradient of H2O:CH3CN:CF3CO2H—65:35:0.1 to 45:55:0.1, then with preparative thin layer chromatography, eluting with a gradient of EtOAc:hexanes—50:50 to 70:30, to give the title compound. MS: m/z=580 (M+1). HRMS: m/z=580.2542 (M+1); calculated m/z=580.2519 (M+1) for C34H31F2N5O2.

Workup

  1. temperaturecooled
  2. filtrationfiltered through a plug of Celite
  3. washwashing with EtOAc
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was first purified by HPLC
  6. washeluting with a gradient of H2O
  7. washCH3CN:CF3CO2H—65:35:0.1 to 45:55:0.1, then with preparative thin layer chromatography, eluting with a gradient of EtOAc

Sources & evidence

ORD record
ord-977412202d6b493dacc7c36d503ce996
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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