Cyclopropylamine → tert-Butyl (2-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl(2-methoxyethyl)carbamate

HRID 409978Notes

Reaction equation

HRID 409978 reaction equation
[C:1]([O:5][C:6](=[O:37])[N:7]([CH2:12][C:13]1[N:17]([CH3:18])[C:16]([C:19]2[S:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][C:25]=3[O:28][C:29]3[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][C:30]=3[F:36])[CH:20]=2)=[N:15][CH:14]=1)[CH2:8][CH2:9][O:10][CH3:11])([CH3:4])([CH3:3])[CH3:2].ClC(Cl)(O[C:42](=[O:48])OC(Cl)(Cl)Cl)Cl.CC[N:52]([CH:56]([CH3:58])[CH3:57])C(C)C.C1(N)CC1>>[C:1]([O:5][C:6](=[O:37])[N:7]([CH2:12][C:13]1[N:17]([CH3:18])[C:16]([C:19]2[S:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][C:25]=3[O:28][C:29]3[CH:34]=[CH:33][C:32]([NH:35][C:42]([NH:52][CH:56]4[CH2:58][CH2:57]4)=[O:48])=[CH:31][C:30]=3[F:36])[CH:20]=2)=[N:15][CH:14]=1)[CH2:8][CH2:9][O:10][CH3:11])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 57919490tert-Butyl (2-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl(2-methoxyethyl)carbamate

Product 1

HCID 58236627tert-Butyl (2-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl(2-methoxyethyl)carbamateYield 92%

Procedure

To a solution of the aniline 46 (400 mg, 0.758 mmol) was added triphosgene (1125 mg, 5 eq, 3.79 mmol) and iPr2NEt (490 mg, 5 eq, 3.79 mmol) and the reaction mixture was stirred at RT for an hour. Cyclopropylamine (6103 mg, 141 eq, 107 mmol) was added and the reaction mixture was stirred at RT overnight. The mixture was concentrated then diluted with DCM and washed with water. The organic phase was collected, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography (eluent 20% MeOH in EtOAc) to afford the desired compound 347 as a yellow oil (426 mg, 92% yield). MS (m/z)=611.4 (M+H).

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. concentrationThe mixture was concentrated
  3. additionthen diluted with DCM
  4. washwashed with water
  5. customThe organic phase was collected
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography (eluent 20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-f5c7734fe60345608b4dd09c5228b7c5
Source dataset
uspto-grants-2014_06
Patent number
US08759522B2

Reaction notes

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