Diisopropylethylamine → (5)-tert-butyl 2-allyl-3-(2-(3-(3-iodophenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylamino)-2-oxoethyl)-1H-indole-1-carboxylate

HRID 1471642Notes

Reaction equation

HRID 1471642 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([CH2:8][C@H:9](NC(=O)OC(C)(C)C)[C:10]([N:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH3:13])=[O:11])[CH:5]=[CH:6][CH:7]=1.[CH2:30]([C:33]1[N:34]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C:35]2[C:40]([C:41]=1[CH2:42][C:43](O)=[O:44])=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:31]=[CH2:32].CC[N:55](C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(O)(C(F)(F)F)=O.CN(C=O)C.CCOC(C)=O>[CH2:30]([C:33]1[N:34]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C:35]2[C:40]([C:41]=1[CH2:42][C:43]([NH:55][C@@H:9]([CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([I:1])[CH:3]=1)[C:10]([N:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[CH3:13])=[O:11])=[O:44])=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:31]=[CH2:32]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 902812522-(2-allyl-1-(tert-butoxycarbonyl)-1H-indol-3-yl)acetic acidHCID 90289973(S)-tert-butyl 3-(3-iodophenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate

Product 1

HCID 90281577(5)-tert-butyl 2-allyl-3-(2-(3-(3-iodophenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylamino)-2-oxoethyl)-1H-indole-1-carboxylate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6422Trifluoroacetic acidSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-tert-butyl 3-(3-iodophenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate (556 mg, 1.09 mml) in TFA (3 ml) was stirred for 10 minutes. The solvent was removed in vacuo. 2-(2-allyl-1-(tert-butoxycarbonyl)-1H-indol-3-yl)acetic acid (343 mg, 1.09 mmol), DIEA (0.38 ml, 2.18 mmol) and O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 414.4 mg, 1.09 mmol) were dissolved in DMF. After 10 minutes, the solution was added to TFA salt. The reaction was stirred for 2 hours at room temperature. The mixture was diluted with EtOAc (100 ml) and washed with brine (2×50 ml). The organic layer was dried over Na2SO4, filtered and concentrated. The oily crude product was introduced to a silica gel loading column and purified by column chromatography (20-50% EtOAc/hexanes) to provide the desired product (620 mg, 0.94 mmol. MS (m/z) 660 [M+H]+.

Workup

  1. customThe solvent was removed in vacuo
  2. washwashed with brine (2×50 ml)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe oily crude product was introduced to a silica gel loading column
  7. custompurified by column chromatography (20-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ff24bf3d0ce24756b63c6c91490d386e
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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