Tri-o-tolylphosphine → (E)-3-(1,2,3,4,5,6-hexahydropyrido[2,3-b][1,5]diazocin-8-yl)-N-methyl-N-((3-methylbenzofuran-2-yl)methyl)acrylamide

HRID 340842Notes

Reaction equation

HRID 340842 reaction equation
Br[C:2]1[CH:20]=[N:19][C:5]2[NH:6][CH2:7][CH2:8][CH2:9][N:10](C(OC(C)(C)C)=O)[CH2:11][C:4]=2[CH:3]=1.[CH3:21][N:22]([CH2:27][C:28]1[O:29][C:30]2[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=2[C:32]=1[CH3:33])[C:23](=[O:26])[CH:24]=[CH2:25].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH:6]1[CH2:7][CH2:8][CH2:9][NH:10][CH2:11][C:4]2[CH:3]=[C:2](/[CH:25]=[CH:24]/[C:23]([N:22]([CH3:21])[CH2:27][C:28]3[O:29][C:30]4[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=4[C:32]=3[CH3:33])=[O:26])[CH:20]=[N:19][C:5]1=2

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 57742103N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamideHCID 59332831tert-butyl 8-bromo-1,2,3,4-tetrahydropyrido[2,3-b][1,5]diazocine-5(6H)-carboxylate

Product 1

HCID 24891659(E)-3-(1,2,3,4,5,6-hexahydropyrido[2,3-b][1,5]diazocin-8-yl)-N-methyl-N-((3-methylbenzofuran-2-yl)methyl)acrylamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 86641869DMF propionitrileSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of tert-butyl 8-bromo-1,2,3,4-tetrahydropyrido[2,3-b][1,5]diazocine-5(6H)-carboxylate (45 mg, 0.13 mmol), N-methyl-N-((3-methylbenzofuran-2-yl)methyl)acrylamide (90 mg, 0.39 mmol) and (i-Pr)2EtN (0.11 mL, 0.66 mmol) in 3.75 mL of DMF:propionitrile (4:1) was de-oxygenated with Ar for 30 min. The mixture was treated with Pd(OAc)2 (3.0 mg, 0.013 mmol) and P(o-tol)3 (8.0 mg, 0.926 mmol) then heated to 110° C. for 20 h. The hot mixture was filtered through a pad of celite and washed with ethyl acetate 2×20 mL. The filtrate was concentrated in vacuo to obtain crude brown oil product. The resulting crude product was subjected to prep HPLC purification to obtain pure product as an off-white solid. Yield 39 mg (60%); ESI MS m/z 491 [C28H34N4O4+H]+

Workup

  1. filtrationThe hot mixture was filtered through a pad of celite
  2. washwashed with ethyl acetate 2×20 mL
  3. concentrationThe filtrate was concentrated in vacuo
  4. customto obtain crude brown oil product
  5. customHPLC purification
  6. customto obtain pure product as an off-white solid

Sources & evidence

ORD record
ord-7ce586206e4347e59e6cad8e97b930ab
Source dataset
uspto-grants-2014_11
Patent number
US08895545B2

Reaction notes

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