Diisopropylethylamine → 7-{2-[(7-fluoro-1H-indol-3-ylmethyl)-amino]-benzoylamino}-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 969682Notes

Reaction equation

HRID 969682 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH2:11][NH:12][C:13]1[CH:21]=[CH:20][CH:19]=[CH:18][C:14]=1[C:15]([OH:17])=O.[C:22]([O:26][C:27]([N:29]1[CH2:38][C:37]([CH3:40])([CH3:39])[C:36]2[C:31](=[CH:32][C:33]([NH2:41])=[CH:34][CH:35]=2)[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:22]([O:26][C:27]([N:29]1[CH2:38][C:37]([CH3:40])([CH3:39])[C:36]2[C:31](=[CH:32][C:33]([NH:41][C:15](=[O:17])[C:14]3[CH:18]=[CH:19][CH:20]=[CH:21][C:13]=3[NH:12][CH2:11][C:7]3[C:6]4[C:10](=[C:2]([F:1])[CH:3]=[CH:4][CH:5]=4)[NH:9][CH:8]=3)=[CH:34][CH:35]=2)[CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21959561Tert-butyl 7-amino-4,4-dimethyl-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 695103892-[(7-fluoro-1H-indol-3-ylmethyl)-amino]-benzoic acid

Product 1

HCID 590174517-{2-[(7-fluoro-1H-indol-3-ylmethyl)-amino]-benzoylamino}-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-[(7-fluoro-1H-indol-3-ylmethyl)-amino]-benzoic acid (Step A, 200 mg, 0.70 mmol), 7-amino-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (194 mg, 0.70 mmol), TBTU (247 mg, 0.80 mmol), and DIEA (0.25 mL, 1.4 mmol) in CH2Cl2 (5 mL) was stirred at RT under N2 atmosphere for 16 h. The mixture was diluted with CH2Cl2 (5 mL) and extracted with water (2×10 mL). The crude material was purified with flash chromatography (SiO2, 15% EtOAc/hexane) to give a yellow solid. MS (ES+) 543.1. (M+H)+. Calc'd for C32H35FN4O3-542.24.

Workup

  1. extractionextracted with water (2×10 mL)
  2. customThe crude material was purified with flash chromatography (SiO2, 15% EtOAc/hexane)
  3. customto give a yellow solid

Sources & evidence

ORD record
ord-c5123ddc50ce472db2deb499513d23a6
Source dataset
uspto-grants-2007_12
Patent number
US07307088B2

Reaction notes

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