Diisopropylethylamine → HCID 42640738, compound

HRID 2280033Notes

Reaction equation

HRID 2280033 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]3([CH2:14][CH2:13]3)[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:64]([N:71]1[CH2:77][CH2:76][CH2:75][N:74]([CH:78]2[CH2:83][CH2:82][CH:81]([NH2:84])[CH2:80][CH2:79]2)[CH2:73][CH2:72]1)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1>CN(C=O)C>[CH2:64]([N:71]1[CH2:77][CH2:76][CH2:75][N:74]([CH:78]2[CH2:83][CH2:82][CH:81]([NH:84][C:26](=[O:27])[C:25]3[CH:29]=[CH:30][C:22]([NH:21][C:19]4[N:18]=[CH:17][C:8]5[N:9]([CH3:16])[C:10](=[O:15])[C:11]6([CH2:13][CH2:14]6)[CH2:12][N:6]([CH:1]6[CH2:2][CH2:3][CH2:4][CH2:5]6)[C:7]=5[N:20]=4)=[C:23]([O:31][CH3:32])[CH:24]=3)[CH2:80][CH2:79]2)[CH2:73][CH2:72]1)[C:65]1[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 576350144-[(9-cyclopentyl-6,7,8,9-tetrahydro-5-methyl-6-oxospiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclopropan]-2-yl)amino]-3-methoxybenzoic acid2×HCID 58154083HCID 58154083, compound2×

Product 1

HCID 42640738HCID 42640738, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-(9′-Cyclopentyl-5′-methyl-6′-oxo-5′,6′,8′,9′-tetrahydrospiro[cyclopropane-1,7′-pyrimido[4,5-b][1,4]diazepine]-2′-ylamino)-3-methoxybenzoic acid (Intermediate 5) (66 mg, 0.15 mmol, 1 eq), DIPEA (52 μl, 0.3 mmol, 2 eq) and TBTU (54 mg, 0.17 mmol, 1.1 eq) were added to 1 mL DMF and the resulting solution was stirred at rt for 20 min before the addition of 4-(4-benzyl-1,4-diazepan-1-yl)cyclohexanamine (Intermediate 16) (54 mg, 0.19 mmol, 1.27 eq) dissolved in DMF (0.5 mL). The RM was then stirred at rt for 2 hours before purifying by preparative RP-HPLC-MS (Preparative—5) to provide N-(4-(4-benzyl-1,4-diazepan-1-yl)cyclohexyl)-4-(9′-cyclopentyl-5′-methyl-6′-oxo-5′,6′,8′,9′-tetrahydrospiro[cyclopropane-1,7′-pyrimido[4,5-b][1,4]diazepine]-2′-ylamino)-3-methoxybenzamide as a mixture cis and trans isomers (off-white solid, 33 mg, 31%).

Workup

  1. custombefore purifying by preparative RP-HPLC-MS (Preparative—5)

Sources & evidence

ORD record
ord-607b61e222134ffb907647294aef25c8
Source dataset
uspto-grants-2015_09
Patent number
US09133199B2

Reaction notes

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