Trifluoroacetic acid → HCID 178492708, compound

HRID 2280028Notes

Reaction equation

HRID 2280028 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]3([CH2:16][CH2:15][CH2:14]3)[CH2:8][N:7]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:6]=2[N:22]=1.[NH2:23][C:24]1[CH:48]=[CH:47][C:27]([C:28]([NH:30][C@H:31]2[CH2:36][CH2:35][C@H:34]([N:37]3[CH2:42][CH2:41][N:40]([CH2:43][CH:44]4[CH2:46][CH2:45]4)[CH2:39][CH2:38]3)[CH2:33][CH2:32]2)=[O:29])=[CH:26][C:25]=1[O:49][CH3:50].C(O)(C(F)(F)F)=O>>[CH:17]1([N:7]2[CH2:8][C:9]3([CH2:16][CH2:15][CH2:14]3)[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:23][C:24]4[CH:48]=[CH:47][C:27]([C:28]([NH:30][C@H:31]5[CH2:32][CH2:33][C@H:34]([N:37]6[CH2:42][CH2:41][N:40]([CH2:43][CH:44]7[CH2:46][CH2:45]7)[CH2:39][CH2:38]6)[CH2:35][CH2:36]5)=[O:29])=[CH:26][C:25]=4[O:49][CH3:50])=[N:22][C:6]2=3)[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 579698622'-Chloro-9'-cyclopentyl-5'-methyl-8',9'-dihydrospiro[cyclobutane-1,7'-pyrimido[4,5-b][1,4]diazepin]-6'(5'H)-one2×HCID 178492706HCID 178492706, compound2×

Product 1

HCID 178492708HCID 178492708, compound

Procedure

2′-Chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclobutane-1,7′-pyrimido[4,5-b][1,4]diazepin]-6′(5′H)-one (Intermediate 4) (0.065 g, 0.2 mmol, 1 eq), 4-amino-N-(trans-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide (Intermediate 11) (0.24 g, 0.6 mmol, 3 eq) and TFA (75 μL, 1 mmol, 5 eq) in TFE (6 mL) were heated to reflux together 40 hours. RM was concentrated in vacuo and the residue was partitioned between EtOAc and saturated sodium hydrogen carbonate. The organic layer was separated, washed with saturated brine and concentrated in vacuo to a residue that was purified by preparative RP-HPLC-MS (Preparative—1) to give 4-(9′-cyclopentyl-5′-methyl-6′-oxo-5′,6′,8′,9′-tetrahydrospiro[cyclobutane-1,7′-pyrimido[4,5-b][1,4]diazepine]-2′-ylamino)-N-((trans)-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide.

Workup

  1. temperatureto reflux together 40 hours
  2. concentrationRM was concentrated in vacuo
  3. customthe residue was partitioned between EtOAc and saturated sodium hydrogen carbonate
  4. customThe organic layer was separated
  5. washwashed with saturated brine
  6. concentrationconcentrated in vacuo to a residue that
  7. customwas purified by preparative RP-HPLC-MS (Preparative—1)

Sources & evidence

ORD record
ord-be56a2dab62140e0be5d32cf973d2d76
Source dataset
uspto-grants-2015_09
Patent number
US09133199B2

Reaction notes

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