Diisopropylethylamine → 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

HRID 331509Notes

Reaction equation

HRID 331509 reaction equation
[NH2:1][C:2]1[C:3]([C:19]([NH:21][NH2:22])=[O:20])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([C:14]([C:17]#[N:18])([CH3:16])[CH3:15])[CH:9]=2)=[CH:6][N:7]=1.[C:23]([O:27][C:28]([N:30]1[CH2:39][CH2:38][C:37]2[C:32](=[CH:33][CH:34]=[C:35]([C:40](O)=[O:41])[CH:36]=2)[CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C(N(C(C)C)CC)(C)C.F[B-](F)(F)F.N1(OC(=[N+](C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[NH2:1][C:2]1[C:3]([C:19]([NH:21][NH:22][C:40]([C:35]2[CH:36]=[C:37]3[C:32](=[CH:33][CH:34]=2)[CH2:31][N:30]([C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:29])[CH2:39][CH2:38]3)=[O:41])=[O:20])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([C:14]([C:17]#[N:18])([CH3:16])[CH3:15])[CH:9]=2)=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 113578872-(tert-Butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acidHCID 708186113-Amino-6-[2-(1-cyano-1-methyl-ethyl)-4-pyridyl]pyrazine-2-carbohydrazide

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-amino-6-[2-(1-cyano-1-methyl-ethyl)-4-pyridyl]pyrazine-2-carbohydrazide (49.5 mg, 0.1665 mmol), 2-tert-butoxycarbonyl-3,4-dihydro-1H-isoquinoline-6-carboxylic acid (50.80 mg, 0.1832 mmol), diisopropyl ethyl amine (25.82 mg, 34.80 μL, 0.1998 mmol) and (benzotriazol-1-yloxy-dimethylamino-methylene)-dimethyl-ammonium tetrafluoroborate (58.82 mg, 0.1832 mmol) was stirred at ambient temperature in N,N-dimethyl formamide (495.0 μL) for 1 hour. The reaction mixture was partitioned between water and ethyl acetate. The combined organic extracts were washed with aqueous saturated sodium bicarbonate, then 0.5 N hydrochloric acid, followed by brine. The organic extracts were then dried over MgSO4 and concentrated in vacuo to give the sub-titled product. (92 mg, 99.27%) LC/MS m/z 557.2 [M+H]+.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. washThe combined organic extracts were washed with aqueous saturated sodium bicarbonate
  3. dry with materialThe organic extracts were then dried over MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cf36c8de8b6141c7900953e6261bf3e4
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

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