Triethylamine → HCID 58379677, compound

HRID 1038986Notes

Reaction equation

HRID 1038986 reaction equation
[CH2:1]([N:8]([CH2:15][C:16]#[CH:17])[C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:19]1[CH:20]=[C:21]2[C:34](=[CH:35][CH:36]=1)[CH2:33][C:23]1([C:31]3[C:26](=[N:27][CH:28]=[CH:29][CH:30]=3)[NH:25][C:24]1=[O:32])[CH2:22]2.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>CN(C=O)C.O.CCOC(C)=O.[Cu]I.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.[Pd].[Pd]>[CH2:1]([N:8]([CH2:15][C:16]#[C:17][C:19]1[CH:20]=[C:21]2[C:34](=[CH:35][CH:36]=1)[CH2:33][C:23]1([C:31]3[C:26](=[N:27][CH:28]=[CH:29][CH:30]=3)[NH:25][C:24]1=[O:32])[CH2:22]2)[C:9](=[O:14])[C:10]([CH3:12])([CH3:13])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

11

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphine2×HCID 58379680HCID 58379680, compoundHCID 58379696HCID 58379696, compound2×

Product 1

HCID 58379677HCID 58379677, compound

Reagents, catalysts & solvents 6

HCID 23938PalladiumCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 10952654Pd[(o-tol)3P]2CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a heterogeneous mixture of N-benzyl-2,2-dimethyl-N-prop-2-yn-1-ylpropanamide (222 mg, 0.968 mmol, from Step A), 5-bromo-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (218 mg, 0.692 mmol, described in Intermediate 5), CuI (7.0 mg, 0.35 mmol), tris(2-methylphenyl)phosphine (84.0 mg, 0.277 mmol) and triethylamine (0.6 mL), in DMF (0.8 mL), while under a nitrogen atmosphere, was added bis[tris(2-methylphenyl)phosphine]palladium (II) chloride (109 mg, 0.138 mmol). The reaction mixture was then heated to 50° C. for 20 hours. An additional amount of alkyne (2 drops), tris(2-methylphenyl)phosphine (40 mg) and palladium salt (50 mg) was added and the reaction was allowed to stir an additional 2 hours. The reaction was then diluted with water and EtOAc. The organics were separated and then washed with water (×5), then with brine (×1). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo to provide a residue. The residue was then applied to a silica gel column for partial purification, eluting with a gradient of 15-80% EtOAc in hexanes to give slightly impure title compound. This impure material was then applied to a silica gel column for purification, eluting with a gradient of 1-7% MeOH in DCM to give the title compound. MS: m/z=464 (M+1). Human CGRP receptor binding Ki=20 nM. HRMS: m/z=464.2346; calculated m/z=464.2333 for C30H30N3O2.

Workup

  1. customThe organics were separated
  2. washwashed with water (×5)
  3. dry with materialThe organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue
  7. customThe residue was then applied to a silica gel column for partial purification
  8. washeluting with a gradient of 15-80% EtOAc in hexanes

Sources & evidence

ORD record
ord-f54aa16f04dc4370829fcac943c71e7d
Source dataset
uspto-grants-2013_10
Patent number
US08552023B2

Reaction notes

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