Iodine → tert-butyl 6-(5-(3-amino-6-(2-(2-cyanopropan-2-yl)pyridin-4-yl)pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 331510Notes

Reaction equation

HRID 331510 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.II.C(N(CC)CC)C.[NH2:29][C:30]1[C:31]([C:47]([NH:49][NH:50][C:51]([C:53]2[CH:54]=[C:55]3[C:60](=[CH:61][CH:62]=2)[CH2:59][N:58]([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:57][CH2:56]3)=[O:52])=O)=[N:32][C:33]([C:36]2[CH:41]=[CH:40][N:39]=[C:38]([C:42]([C:45]#[N:46])([CH3:44])[CH3:43])[CH:37]=2)=[CH:34][N:35]=1>ClCCl>[NH2:29][C:30]1[C:31]([C:47]2[O:52][C:51]([C:53]3[CH:54]=[C:55]4[C:60](=[CH:61][CH:62]=3)[CH2:59][N:58]([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:57][CH2:56]4)=[N:50][N:49]=2)=[N:32][C:33]([C:36]2[CH:41]=[CH:40][N:39]=[C:38]([C:42]([C:45]#[N:46])([CH3:43])[CH3:44])[CH:37]=2)=[CH:34][N:35]=1

Participants

6

Reactant 4

HCID 807IodineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 70819338tert-butyl 6-[[[3-amino-6-[2-(1-cyano-1-methyl-ethyl)-4-pyridyl]pyrazine-2-carbonyl]amino]carbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate

Product 1

HCID 70856413tert-butyl 6-(5-(3-amino-6-(2-(2-cyanopropan-2-yl)pyridin-4-yl)pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

PS—PPh3 (145.6 mg, 0.3042 mmol) was suspended in dichloromethane (6.269 mL). Iodine (77.21 mg, 15.66 μL, 0.3042 mmol) was added and the mixture was stirred for 10 minutes before triethyl amine (63.10 mg, 86.91 μL, 0.6236 mmol) was added. After 5 minutes tert-butyl 6-[[[3-amino-6-[2-(1-cyano-1-methyl-ethyl)-4-pyridyl]pyrazine-2-carbonyl]amino]carbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate (92 mg, 0.1521 mmol) was added as a solution in dichloromethane (3.919 mL) the mixture was stirred at ambient temperature for 1 hour. The resin was filtered off and the filtrate was washed with aqueous saturated sodium bicarbonate. The extracted organic phase was then dried over MgSO4 and concentrated in vacuo. The residue was taken onto the next step as is. (118.7 mg, assumed 100% yield). LC/MS m/z 539.2 [M+H]+.

Workup

  1. additionwas added
  2. filtrationThe resin was filtered off
  3. washthe filtrate was washed with aqueous saturated sodium bicarbonate
  4. dry with materialThe extracted organic phase was then dried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7fc349a745f741158199681eea686488
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

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