Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → tert-butyl 1-(1-(4-chlorophenyl)-2-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)cyclopropylcarbamate

HRID 625076Notes

Reaction equation

HRID 625076 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[CH3:27][C@H:28]1[C:36]2[C:35]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[N:34][CH:33]=[N:32][C:31]=2[CH2:30][S:29]1.[C:43]([O:47][C:48]([NH:50][C:51]1([CH:54]([C:58]2[CH:63]=[CH:62][C:61]([Cl:64])=[CH:60][CH:59]=2)[C:55](O)=[O:56])[CH2:53][CH2:52]1)=[O:49])([CH3:46])([CH3:45])[CH3:44]>C(Cl)Cl>[Cl:64][C:61]1[CH:62]=[CH:63][C:58]([CH:54]([C:51]2([NH:50][C:48](=[O:49])[O:47][C:43]([CH3:45])([CH3:44])[CH3:46])[CH2:52][CH2:53]2)[C:55]([N:40]2[CH2:41][CH2:42][N:37]([C:35]3[C:36]4[C@H:28]([CH3:27])[S:29][CH2:30][C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:38][CH2:39]2)=[O:56])=[CH:59][CH:60]=1

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674591692-(1-(Tert-butoxycarbonylamino)cyclopropyl)-2-(4-chlorophenyl)acetic acidHCID 67459940HCID 67459940, compound

Product 1

HCID 67457668tert-butyl 1-(1-(4-chlorophenyl)-2-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)cyclopropylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

HBTU (0.097 mmol, 47 mg) was added to a solution of (S)-5-methyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (30 mg, 0.097 mmol) and 2-(1-(tert-butoxycarbonylamino)cyclopropyl)-2-(4-chlorophenyl)acetic acid (0.097 mmol) in DCM (5 mL) and TEA (5 mL). The mixture was stirred at room temperature for 6 hours. The solvent was removed, and the residue was subject to column chromatography, eluted by DCM/MeOH (50:1) to give tert-butyl 1-(1-(4-chlorophenyl)-2-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)cyclopropylcarbamate LCMS: 544.0 [M-Boc+H+] (APCI+); Rf: 3.49 min. The tert-butyl 1-(1-(4-chlorophenyl)-2-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)cyclopropylcarbamate was deprotected using procedures described previously to give 2-(1-aminocyclopropyl)-2-(4-chlorophenyl)-1-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)ethanone. Rf: 2.24 min.

Workup

  1. customThe solvent was removed
  2. washeluted by DCM/MeOH (50:1)

Sources & evidence

ORD record
ord-89ec2295fdb74b0885fcf5222f96b5b2
Source dataset
uspto-grants-2016_04
Patent number
US09303040B2

Reaction notes

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