Tri-o-tolylphosphine → HCID 24891658, compound

HRID 1880014Notes

Reaction equation

HRID 1880014 reaction equation
Br[C:2]1[CH:14]=[N:13][C:5]2[NH:6][C:7](=[O:12])[CH2:8][CH2:9][CH:10]([OH:11])[C:4]=2[CH:3]=1.[CH3:15][N:16]([CH2:21][C:22]1[O:23][C:24]2[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=2[C:26]=1[CH3:27])[C:17](=[O:20])[CH:18]=[CH2:19].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.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:11][CH:10]1[CH2:9][CH2:8][C:7](=[O:12])[NH:6][C:5]2[N:13]=[CH:14][C:2](/[CH:19]=[CH:18]/[C:17]([N:16]([CH3:15])[CH2:21][C:22]3[O:23][C:24]4[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=4[C:26]=3[CH3:27])=[O:20])=[CH:3][C:4]1=2

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 57742103N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamideHCID 59332860HCID 59332860, compound

Product 1

HCID 24891658HCID 24891658, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of 3-bromo-5-hydroxy-6,7-dihydro-5H-pyrido[2,3-b]azepin-8(9H)-one (40 mg, 0.16 mmol), N-methyl-N-((3-methylbenzofuran-2-yl)methyl)acrylamide (71 mg, 0.31 mmol) and (i-Pr)2EtN (0.14 mL, 0.78 mmol) in 3 mL of DMF) was de-oxygenated with Ar for 30 min in a microwave reaction vial. The mixture was treated with Pd(OAc)2 (4.0 mg, 0.02 mmol) and P(o-tol)3 (9.0 mg, 0.04 mmol) then heated to 130° C. for 5 min in the microwave. The hot mixture was filtered through a pad of celite and washed liberally with ethyl acetate. The filtrate was diluted with 20 mL H2O then extracted with 2×20 mL ethyl acetate. The resulting crude product was subjected to prep HPLC purification to yield 47 mg of product (75% pure). A second prep HPLC purification was performed to obtain pure product as a fluffy white powder. Yield 5.1 mg (8%); 1H NMR (400 MHz, CDCl3) δ 8.31 (s, 1H), 8.09 (s, 1H), 7.56 (d, J=7.4 Hz, 1H), 7.47 (m, 2H), 7.35-7.21 (m, 3H), 7.14 (d, J=15.2 Hz, 1H), 5.60 (s, 1H), 4.77 (s, 2H), 3.17 (s, 3H), 2.65 (s, 3H), 2.26 (m, 4H); ESI MS m/z 406 [C23H23N3O4+H]+

Workup

  1. customwas de-oxygenated with Ar for 30 min in a microwave reaction vial
  2. filtrationThe hot mixture was filtered through a pad of celite
  3. washwashed liberally with ethyl acetate
  4. additionThe filtrate was diluted with 20 mL H2O
  5. extractionthen extracted with 2×20 mL ethyl acetate
  6. customHPLC purification

Sources & evidence

ORD record
ord-79bcd60db8a64393935f91f94c5317f3
Source dataset
uspto-grants-2012_11
Patent number
US08318720B2

Reaction notes

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